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The emerging epidemic of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global public health crisis. However, the phylogenetic affiliation and pathotypic status of CRKP strains in the host colonization period under consistent antibiotic treatments are not well characterized. In this study, a 5-year tracking study was performed, in which a patient admitted to an intensive care unit was recruited and then screened for the carriage of CRKP based on microbiological culture. Nine isolates from the sputum or stool samples were acquired and subjected to real-time whole-genome sequencing, antimicrobial susceptibility testing, Galleria mellonella larval infection, and epithelial cell invasion assay. All nine isolates showed phenotypic resistance to carbapenems, quinolones, and aminoglycosides. Altogether, blaKPC-2 and 10 other antibiotic resistance genes were identified and all nine CRKP isolates exhibited low virulence with more than 38 virulence factors. All but one variant belonged to ST11 with a novel sequence type, differing at the phoE locus. The isolates shared the same plasmid replicon type, prophages, and capsular serotype (K47) with few single-nucleotide polymorphism variations, consistent with epidemiological clones. Furthermore, these CRKP isolates displayed the ability of moderate invasion of lung epithelial cells. Meanwhile, a deficiency of chromosomal type IV secretion system-related gene cluster was detected after 2 years of carriage. Our findings demonstrated that low-virulence CRKP clones could colonize in the gut and respiratory tract under multiple antibiotic stresses, suggesting the strong colonization adaptability of CRKP to the host. Ethical approval was given by The Second Affiliated Hospital of Zhejiang University, School of Medicine, (2018-039).
Zhiqiang Yang; Qiaoling Sun; Shang Chen; Shuangyang Ding; Rong Zhang; Kui Zhu. Genomic and Phenotypic Analysis of Persistent Carbapenem-Resistant Klebsiella pneumoniae Isolates from a 5-Year Hospitalized Patient. Microbial Drug Resistance 2021, 27, 1117 -1125.
AMA StyleZhiqiang Yang, Qiaoling Sun, Shang Chen, Shuangyang Ding, Rong Zhang, Kui Zhu. Genomic and Phenotypic Analysis of Persistent Carbapenem-Resistant Klebsiella pneumoniae Isolates from a 5-Year Hospitalized Patient. Microbial Drug Resistance. 2021; 27 (8):1117-1125.
Chicago/Turabian StyleZhiqiang Yang; Qiaoling Sun; Shang Chen; Shuangyang Ding; Rong Zhang; Kui Zhu. 2021. "Genomic and Phenotypic Analysis of Persistent Carbapenem-Resistant Klebsiella pneumoniae Isolates from a 5-Year Hospitalized Patient." Microbial Drug Resistance 27, no. 8: 1117-1125.
Pseudomonas aeruginosa is one of the most common opportunistic pathogens, which causes severe nosocomial infections because of its well-known multidrug-resistance and hypervirulence. It is critical to curate routinely the epidemic P. aeruginosa clones encountered in the clinic. The aim of the present study was to investigate the connection between virulence factors and antimicrobial resistance profiles in epidemic clones. Herein, we found that ST463 (O4), ST1212 (O11), and ST244 (O5) were prevalent in 30 isolates derived from non-cystic fibrosis patients, based on multilocus sequence type (MLST) and serotype analysis. All isolates were multidrug-resistant (MDR) and each was resistance to at least three classes of antibiotics in antimicrobial susceptibility tests, which was consistent with the presence of the abundant resistance genes, such as bla OXA–50, bla PAO, aph(3′), catB7, fosA, crpP, and bla KPC–2. Notably, all bla KPC–2 genes were located between ISKpn6-like and ISKpn8-like mobile genetic elements. In addition, classical exotoxins encoded by exoU, exoS, and pldA were present in 43.44% (13/40), 83.33% (25/30), and 70% (21/30) of the isolates, respectively. The expression of phz operons encoding the typical toxin, pyocyanin, was observed in 60% of isolates (18/30) and was quantified using triple quadrupole liquid chromatograph mass (LC/MS) assays. Interestingly, compared with other MLST types, all ST463 isolates harbored exoU, exoS and pldA, and produced pyocyanin ranging from 0.2 to 3.2 μg/mL. Finally, we evaluated the potential toxicity of these isolates using hemolysis tests and Galleria mellonella larvae infection models. The results showed that ST463 isolates were more virulent than other isolates. In conclusion, pyocyanin-producing ST463 P. aeruginosa, carrying diverse virulence genes, is a potential high-risk clone.
Yanyan Hu; Wenjing Peng; Yifan Wu; Hui Li; Qi Wang; Huahua Yi; Rong Zhang; Bing Shao; Kui Zhu. A Potential High-Risk Clone of Pseudomonas aeruginosa ST463. Frontiers in Microbiology 2021, 12, 1 .
AMA StyleYanyan Hu, Wenjing Peng, Yifan Wu, Hui Li, Qi Wang, Huahua Yi, Rong Zhang, Bing Shao, Kui Zhu. A Potential High-Risk Clone of Pseudomonas aeruginosa ST463. Frontiers in Microbiology. 2021; 12 ():1.
Chicago/Turabian StyleYanyan Hu; Wenjing Peng; Yifan Wu; Hui Li; Qi Wang; Huahua Yi; Rong Zhang; Bing Shao; Kui Zhu. 2021. "A Potential High-Risk Clone of Pseudomonas aeruginosa ST463." Frontiers in Microbiology 12, no. : 1.
The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure–activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds, α-mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram-positive bacteria, but also restore the susceptibility of colistin against Gram-negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance.
Meirong Song; Ying Liu; Tingting Li; Xiaojia Liu; Zhihui Hao; Shuangyang Ding; Pharkphoom Panichayupakaranant; Kui Zhu; Jianzhong Shen. Plant Natural Flavonoids Against Multidrug Resistant Pathogens. Advanced Science 2021, 8, 2100749 .
AMA StyleMeirong Song, Ying Liu, Tingting Li, Xiaojia Liu, Zhihui Hao, Shuangyang Ding, Pharkphoom Panichayupakaranant, Kui Zhu, Jianzhong Shen. Plant Natural Flavonoids Against Multidrug Resistant Pathogens. Advanced Science. 2021; 8 (15):2100749.
Chicago/Turabian StyleMeirong Song; Ying Liu; Tingting Li; Xiaojia Liu; Zhihui Hao; Shuangyang Ding; Pharkphoom Panichayupakaranant; Kui Zhu; Jianzhong Shen. 2021. "Plant Natural Flavonoids Against Multidrug Resistant Pathogens." Advanced Science 8, no. 15: 2100749.
Foodborne diseases have been witnessing a constant rising trend worldwide, mainly caused by pathogenic microorganisms, such as Bacillus spp., posing a direct threat to public health. The purpose of this study was to evaluate the biological risk of foodborne and probiotic Bacillus spp. in Beijing markets. A total of 55 Bacillus isolates, including 29 B. cereus, 9 B. licheniformis and 7 B. subtilis, mostly found in dairy products (32.7%), were recovered from 106 samples and identified by matrix-assisted laser desorption/ionization mass spectrometry and polymerase chain reaction methods. The susceptibility towards 16 antibiotics was determined using a broth microdilution method. Bacillus showed a high level of resistance to florfenicol (100%), lincomycin (100%), tiamulin (78.2%) and ampicillin (67.3%), while they were all susceptible or intermediate to vancomycin and rifampin. Additionally, we obtained the whole genome of 19 Bacillus strains using high-throughput sequencing, and the rates of resistance genes van, fosB, erm and tet were 57.9%, 57.9%, 21.1% and 26.3%, respectively. Moreover, 100%, 9.1%, 45.5% and 100% of these isolates carried virulence genes nhe, hbl, cytK and entFM, respectively. Lastly, 60% Bacillus strains were positive in hemolysis tests, and 3 B. licheniformis strains displayed an inhibitory activity on the growth of S. aureus ATCC 29213 using agar overlay technique. Our study outlines the characteristics of foodborne Bacillus spp. and provides information for the monitoring of food safety.
Qiao Hu; Yuwen Fang; Jiajia Zhu; Wenjiao Xu; Kui Zhu. Characterization of Bacillus Species from Market Foods in Beijing, China. Processes 2021, 9, 866 .
AMA StyleQiao Hu, Yuwen Fang, Jiajia Zhu, Wenjiao Xu, Kui Zhu. Characterization of Bacillus Species from Market Foods in Beijing, China. Processes. 2021; 9 (5):866.
Chicago/Turabian StyleQiao Hu; Yuwen Fang; Jiajia Zhu; Wenjiao Xu; Kui Zhu. 2021. "Characterization of Bacillus Species from Market Foods in Beijing, China." Processes 9, no. 5: 866.
Opportunistic pathogens frequently cause volatile infections in hosts with compromised immune systems or a disrupted normal microbiota. The commensalism of diverse microorganisms contributes to colonization resistance, which prevents the expansion of opportunistic pathogens. Following microbiota disruption, pathogens promptly adapt to altered niches and obtain growth advantages. Nevertheless, whether and how resident bacteria modulate the growth dynamics of invasive pathogens and the eventual outcome of such infections are still unclear. Here, we utilized birds as a model animal and observed a resident bacterium exacerbating the invasion of Avibacterium paragallinarum (previously Haemophilus paragallinarum) in the respiratory tract. We first found that negligibly abundant Staphylococcus chromogenes, rather than Staphylococcus aureus, played a dominant role in Av. paragallinarum-associated infectious coryza in poultry based on epidemic investigations and in vitro analyses. Furthermore, we determined that S. chromogenes not only directly provides the necessary nutrition factor nicotinamide adenine dinucleotide (NAD+) but also accelerates its biosynthesis and release from host cells to promote the survival and growth of Av. paragallinarum. Last, we successfully intervened in Av. paragallinarum-associated infections in animal models using antibiotics that specifically target S. chromogenes. Our findings show that opportunistic pathogens can hijack commensal bacteria to initiate infection and expansion and suggest a new paradigm to ameliorate opportunistic infections by modulating the dynamics of resident bacteria.
Yifan Wu; Yongqiang Wang; Huiming Yang; Qian Li; Xiaoxia Gong; Guozhong Zhang; Kui Zhu. Resident bacteria contribute to opportunistic infections of the respiratory tract. PLOS Pathogens 2021, 17, e1009436 .
AMA StyleYifan Wu, Yongqiang Wang, Huiming Yang, Qian Li, Xiaoxia Gong, Guozhong Zhang, Kui Zhu. Resident bacteria contribute to opportunistic infections of the respiratory tract. PLOS Pathogens. 2021; 17 (3):e1009436.
Chicago/Turabian StyleYifan Wu; Yongqiang Wang; Huiming Yang; Qian Li; Xiaoxia Gong; Guozhong Zhang; Kui Zhu. 2021. "Resident bacteria contribute to opportunistic infections of the respiratory tract." PLOS Pathogens 17, no. 3: e1009436.
Antibiotic resistance nowadays is spreading much faster than the introduction of new antibiotics into clinical practice. There is an urgent need for potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi provide a promising source for chemical diversity with antibiotic-like molecules. To identify structurally distinct compounds that effectively eradicate MDR pathogens and to control the development of antibiotic resistance, we have reinvestigated equisetin, a previously reported meroterpenoid isolated from a marine sponge-derived fungus. Equisetin exerted efficient antibacterial activities against either MRSA or VRE without detectable high-level resistance. Meanwhile, equisetin, as an antibiotic adjuvant, restores colistin susceptibility to colistin-resistant bacteria toward diverse Gram-negative pathogens. Intriguingly, the low-level equisetin-resistant Staphylococcus aureus displayed collateral sensitivity to multiple classes of existing antibiotics with decreased capacity to produce biofilm. Lastly, equisetin showed efficacy with MRSA in three infected animal models. This work suggests that equisetin derived from marine natural products is a promising lead to overcome antibiotic resistance, providing new insight in future antibiotic discovery and development.
Shang Chen; Dong Liu; Qi Zhang; Peng Guo; Shuangyang Ding; Jianzhong Shen; Kui Zhu; Wenhan Lin. A Marine Antibiotic Kills Multidrug-Resistant Bacteria without Detectable High-Level Resistance. ACS Infectious Diseases 2021, 7, 884 -893.
AMA StyleShang Chen, Dong Liu, Qi Zhang, Peng Guo, Shuangyang Ding, Jianzhong Shen, Kui Zhu, Wenhan Lin. A Marine Antibiotic Kills Multidrug-Resistant Bacteria without Detectable High-Level Resistance. ACS Infectious Diseases. 2021; 7 (4):884-893.
Chicago/Turabian StyleShang Chen; Dong Liu; Qi Zhang; Peng Guo; Shuangyang Ding; Jianzhong Shen; Kui Zhu; Wenhan Lin. 2021. "A Marine Antibiotic Kills Multidrug-Resistant Bacteria without Detectable High-Level Resistance." ACS Infectious Diseases 7, no. 4: 884-893.
Bacteria infected cells acting as “Trojan horses” not only protect bacteria from antibiotic therapies and immune clearance, but also increase the dissemination of pathogens from the initial sites of infection. Antibiotics are hard and insufficient to treat such hidden internalized bacteria, especially multidrug‐resistant (MDR) bacteria. Herein, aggregation‐induced emission luminogens (AIEgens) such as N,N‐diphenyl‐4‐(7‐(pyridin‐4‐yl) benzo [c] [1,2,5] thiadiazol‐4‐yl) aniline functionalized with 1‐bromoethane (TBP‐1) and (3‐bromopropyl) trimethylammonium bromide (TBP‐2) (TBPs) show potent broad‐spectrum bactericidal activity against both extracellular and internalized Gram‐positive pathogens. TBPs trigger reactive oxygen species (ROS)‐mediated membrane damage to kill bacteria, regardless of light irradiation. TBPs effectively kill bacteria without the development of resistance. Additionally, such AIEgens activate mitochondria dependent autophagy to eliminate internalized bacteria in host cells. Compared to the routinely used vancomycin in clinic, TBPs demonstrate comparable efficacy against methicillin‐resistant Staphylococcus aureus (MRSA) in vivo. The studies suggest that AIEgens are promising new agents for the treatment of MDR bacteria associated infections.
Ying Li; Fei Liu; Jiangjiang Zhang; Xiaoye Liu; Peihong Xiao; Haotian Bai; Shang Chen; Dong Wang; Simon H. P. Sung; Ryan T. K. Kwok; Jianzhong Shen; Kui Zhu; Ben Zhong Tang. Efficient Killing of Multidrug‐Resistant Internalized Bacteria by AIEgens In Vivo. Advanced Science 2021, 8, 2001750 .
AMA StyleYing Li, Fei Liu, Jiangjiang Zhang, Xiaoye Liu, Peihong Xiao, Haotian Bai, Shang Chen, Dong Wang, Simon H. P. Sung, Ryan T. K. Kwok, Jianzhong Shen, Kui Zhu, Ben Zhong Tang. Efficient Killing of Multidrug‐Resistant Internalized Bacteria by AIEgens In Vivo. Advanced Science. 2021; 8 (9):2001750.
Chicago/Turabian StyleYing Li; Fei Liu; Jiangjiang Zhang; Xiaoye Liu; Peihong Xiao; Haotian Bai; Shang Chen; Dong Wang; Simon H. P. Sung; Ryan T. K. Kwok; Jianzhong Shen; Kui Zhu; Ben Zhong Tang. 2021. "Efficient Killing of Multidrug‐Resistant Internalized Bacteria by AIEgens In Vivo." Advanced Science 8, no. 9: 2001750.
Natural bisindole alkaloids such as Hyrtinadine A and Alocasin A, which are known to exhibit diverse bioactivities, provide promising chemical scaffolds for drug development. By optimizing the Masuda borylation-Suzuki coupling sequence, a library of various natural product-derived and non-natural (di)azine-bridged bisindoles was created. While unsubstituted bisindoles were devoid of antibacterial activity, 5,5'-chloro derivatives were highly active against methicillin-resistant Staphylococcus aureus (MRSA) and further Gram-positive pathogens at minimal inhibitory concentrations ranging from 0.20 to 0.78 μM. These compounds showed strong bactericidal killing effects but only moderate cytotoxicity against human cell lines. Furthermore, the two front-runner compounds 4j and 4n exhibited potent in vivo efficacy against MRSA in a mouse wound infection model. Although structurally related bisindoles were reported to specifically target pyruvate kinase in MRSA, antibacterial activity of 4j and 4n is independent of pyruvate kinase. Rather, these compounds lead to bacterial membrane permeabilization and cellular efflux of low-molecular-weight molecules.
Nidja Rehberg; Gereon A. Sommer; Daniel Drießen; Marco Kruppa; Emmanuel T. Adeniyi; Shang Chen; Lin Wang; Karina Wolf; Boris O. A. Tasch; Thomas R. Ioerger; Kui Zhu; Thomas J. J. Müller; Rainer Kalscheuer. Nature-Inspired (di)Azine-Bridged Bisindole Alkaloids with Potent Antibacterial In Vitro and In Vivo Efficacy against Methicillin-Resistant Staphylococcus aureus. Journal of Medicinal Chemistry 2020, 63, 12623 -12641.
AMA StyleNidja Rehberg, Gereon A. Sommer, Daniel Drießen, Marco Kruppa, Emmanuel T. Adeniyi, Shang Chen, Lin Wang, Karina Wolf, Boris O. A. Tasch, Thomas R. Ioerger, Kui Zhu, Thomas J. J. Müller, Rainer Kalscheuer. Nature-Inspired (di)Azine-Bridged Bisindole Alkaloids with Potent Antibacterial In Vitro and In Vivo Efficacy against Methicillin-Resistant Staphylococcus aureus. Journal of Medicinal Chemistry. 2020; 63 (21):12623-12641.
Chicago/Turabian StyleNidja Rehberg; Gereon A. Sommer; Daniel Drießen; Marco Kruppa; Emmanuel T. Adeniyi; Shang Chen; Lin Wang; Karina Wolf; Boris O. A. Tasch; Thomas R. Ioerger; Kui Zhu; Thomas J. J. Müller; Rainer Kalscheuer. 2020. "Nature-Inspired (di)Azine-Bridged Bisindole Alkaloids with Potent Antibacterial In Vitro and In Vivo Efficacy against Methicillin-Resistant Staphylococcus aureus." Journal of Medicinal Chemistry 63, no. 21: 12623-12641.
A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds –
Meirong Song; Kui Zhu. A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds. Microbial Cell 2020, 7, 215 -217.
AMA StyleMeirong Song, Kui Zhu. A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds. Microbial Cell. 2020; 7 (8):215-217.
Chicago/Turabian StyleMeirong Song; Kui Zhu. 2020. "A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds." Microbial Cell 7, no. 8: 215-217.
Antibiotic therapy and host cells frequently fail to eliminate invasive bacterial pathogens due to the emergence of antibiotic resistance, resulting in the relapse and recurrence of infections. Bacteria evolve various strategies to persist and survive in epithelial cells, a front‐line barrier of host tissues counteracting invasion; however, it remains unclear how bacteria hijack cellular responses to promote cytoplasmic survival under antibiotic therapy. Here, it is demonstrated that extracellular bacteria show invasive behavior and survive in epithelial cells in both in vivo and in vitro models, to increase antibiotic tolerance. In turn, sublethal levels of antibiotics increase bacterial invasion through promoting the production of bacterial virulence factors. Furthermore, antibiotic treatments interrupt lysosomal acidification in autophagy due to the internalized bacteria, using Bacillus cereus and ciprofloxacin as a model. In addition, it is found that sublethal levels of ciprofloxacin cause mitochondrial dysfunction and reactive oxygen species (ROS) accumulation to impair lysosomal vascular tape ATPase (V‐ATPase) to further promote bacterial persistence. Collectively, these results highlight the potential of host cells mediated antibiotic tolerance, which markedly compromises antibiotic efficacy and worsens the outcomes of infection.
Xiaoye Liu; Fei Liu; Shuangyang Ding; Jianzhong Shen; Kui Zhu. Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells. Advanced Science 2020, 7, 1 .
AMA StyleXiaoye Liu, Fei Liu, Shuangyang Ding, Jianzhong Shen, Kui Zhu. Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells. Advanced Science. 2020; 7 (18):1.
Chicago/Turabian StyleXiaoye Liu; Fei Liu; Shuangyang Ding; Jianzhong Shen; Kui Zhu. 2020. "Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells." Advanced Science 7, no. 18: 1.
Bacillus cereus is a common and ubiquitous foodborne pathogen with an increasing prevalence rate in dairy products in China. High and unmet demands for such products, particularly milk, raise the risk of B. cereus associated contamination. The presence of B. cereus and its virulence factors in dairy products may cause food poisoning and other illnesses. Thus, this review first summarizes the epidemiological characteristics and analytical assays of B. cereus from dairy products in China, providing insights into the implementation of intervention strategies. In addition, the recent achievements on the cytotoxicity and mechanisms of B. cereus are also presented to shed light on the therapeutic options for B. cereus associated infections.
Xiao-Ye Liu; Qiao Hu; Fei Xu; Shuang-Yang Ding; Kui Zhu. Characterization of Bacillus cereus in Dairy Products in China. Toxins 2020, 12, 454 .
AMA StyleXiao-Ye Liu, Qiao Hu, Fei Xu, Shuang-Yang Ding, Kui Zhu. Characterization of Bacillus cereus in Dairy Products in China. Toxins. 2020; 12 (7):454.
Chicago/Turabian StyleXiao-Ye Liu; Qiao Hu; Fei Xu; Shuang-Yang Ding; Kui Zhu. 2020. "Characterization of Bacillus cereus in Dairy Products in China." Toxins 12, no. 7: 454.
Probiotic microbes conferring health benefits to the hosts have attracted great concerns recently. Particularly, spore-forming Bacillus cereus (B. cereus), Gram-positive, aerobic or facultative anaerobic bacteria, have been widely used in probiotic preparations for different purposes, due to their high stability to harsh conditions. Probiotics are generally recognized as safe (GRAS) and showing satisfactory overall safety records till now. However, the safety of each probiotic isolate is not guaranteed. The verification of the absence of mobile antimicrobial resistance genes and virulence factors is a prerequisite for the approval of probiotic candidates, according to the guidelines suggested by the Food and Agriculture Organization (FAO) and World Health Organization (WHO). The role of B. cereus and other members of the B. cereus group in gastrointestinal and non-gastrointestinal diseases has not always gained sufficient attention in the past, particularly in view of their use as probiotics. Therefore, the presence of transferrable antimicrobial resistance genes will endow probiotics as a reservoir with increased ability of emergence and dissemination, during their wide and inadvertent use. Our previous study found that the presence of transferable tetracycline resistance gene tet(45) in a probiotic isolate B. cereus 9i (BC 9i) derived of animal feed additive. The aim of the present work was to systematically characterize this tet(45). The draft assembled genome of BC 9i was first used to analyze the genetic environment of tet(45). Meanwhile, multiple alignment and a maximum likelihood tree were built to conduct the phylogenetic relationship between tet(45) and othertetracycline efflux resistance genes. In addition, the 3D protein structures were predicted to identify differences between Tet(45) and the original Tet(45). Lastly, the tet(45) gene in BC 9i was cloned and transferred into Staphylococcus aureus RN4220 to the minimum inhibitory concentrations, in the presence and absence of classic inhibitors of efflux pumps. The phylogenetic analysis showed that the gene tet(45) in BC 9i was classified as a gene variant of tet(45), belonging to the major facilitator superfamily of membrane transporters. Additionally, the predicted structure of Tet(45) variant was similar to the original Tet(45), both sharing a 14-transmembrane helix core, although they exhibited subtle structural differences in the loop regions and α-helixes. Lastly, the resistance to tetracyclines in tet(45) variant was suppressed in the presence of efflux pump inhibitors. These results indicated that the tet(45) variant in BC 9i encoded a efflux pump against tetracyclines. Collectively, our findings suggest that such probiotic isolates harboring transferable antimicrobial resistance genes may consist a potential risk for public health. It sheds light on the subsequent screening of probiotic candidates and the appropriate application of probiotics for various purposes, to promote and improve One Health.
Yifang Cui; Fuzhou Xu; Shuangyang Ding; Kui Zhu. Characteristics of a transferable tet(45) gene conferring resistance to tetracyclines in probiotic Bacillus cereus. Chinese Science Bulletin 2020, 65, 3619 -3625.
AMA StyleYifang Cui, Fuzhou Xu, Shuangyang Ding, Kui Zhu. Characteristics of a transferable tet(45) gene conferring resistance to tetracyclines in probiotic Bacillus cereus. Chinese Science Bulletin. 2020; 65 (32):3619-3625.
Chicago/Turabian StyleYifang Cui; Fuzhou Xu; Shuangyang Ding; Kui Zhu. 2020. "Characteristics of a transferable tet(45) gene conferring resistance to tetracyclines in probiotic Bacillus cereus." Chinese Science Bulletin 65, no. 32: 3619-3625.
Food safety is always a global issue, due to the increased dissemination of antimicrobial resistance and food poisoning related to foodborne bacterial pathogens. The purpose of this study was to assess the risk of potential foodborne bacteria of beef and mutton in retail stores. A total of 134 samples were collected from 24 local markets in Beijing, including raw and cooked beef or mutton, as well as samples derived from the corresponding environment and human beings. We obtained 674 isolates, of which Klebsiella spp. and Staphylococcus spp. were the dominant bacterial species in the meat samples and the environmental samples, respectively. Additionally, environmental bacteria are common in samples from different sources. Based on the results of antimicrobial sensitivity testing, resistance to tetracycline (with a resistance rate of 47.40%), amoxicillin + clavulanate (47.13%) and erythromycin (28.03%) were the major resistant phenotypes. According to the whole genome analysis, the extended spectrum beta-lactamase genes harboured by two K. pneumoniae strains isolated from cooked and raw beef were located on mobile elements. The major toxin genes of Bacillus cereus and adhesion- or invasion-related virulence factors were also shared among isolates from different sources. These factors pose potential risks to public health and need attention.
Ying Liu; Yifang Cui; Wenjing Peng; Baoyong Huang; Lichao Ma; Min Zheng; Shuangyang Ding; Kui Zhu. Prevalence of pathogens harbouring mobile antimicrobial resistance genes and virulence factors in retail beef and mutton. FEMS Microbiology Letters 2020, 367, 1 .
AMA StyleYing Liu, Yifang Cui, Wenjing Peng, Baoyong Huang, Lichao Ma, Min Zheng, Shuangyang Ding, Kui Zhu. Prevalence of pathogens harbouring mobile antimicrobial resistance genes and virulence factors in retail beef and mutton. FEMS Microbiology Letters. 2020; 367 (12):1.
Chicago/Turabian StyleYing Liu; Yifang Cui; Wenjing Peng; Baoyong Huang; Lichao Ma; Min Zheng; Shuangyang Ding; Kui Zhu. 2020. "Prevalence of pathogens harbouring mobile antimicrobial resistance genes and virulence factors in retail beef and mutton." FEMS Microbiology Letters 367, no. 12: 1.
The rapid emergence and dissemination of multidrug-resistant (MDR) bacterial pathogens pose a serious threat to global healthcare. One particular concern is the carbapenem-resistant Enterobacteriaceae (CRE), a group of Gram-negative bacteria that have evolved resistance to all or nearly all available antibiotics. Coupled with the fact of barren antibiotic development pipeline nowadays, a critical approach is to revitalize existing antibiotics using antibiotic adjuvants. We found a short linear antibacterial peptide (SLAP)-S25 carrying four non-natural amino acids of 2,4-diaminobutanoic acid (Dab), which solely showed weak antibacterial activity but boosted the efficacy of antibiotics covering all major classes, including cefepime, colistin, ofloxacin, rifampicin, tetracycline and vancomycin, against MDR Gram-negative pathogens. Mechanistic studies showed that SLAP-S25 triggers membrane damage by binding to both lipopolysaccharide (LPS) in the outer membrane and phosphatidylglycerol (PG) in bacterial cytoplasmic membrane, to potentiate antibiotic efficacy through collaborative strategies. Lastly, SLAP-S25 effectively enhanced the activity of colistin against MDR Escherichia coli-associated infections in three animal models. Our findings provide a potential therapeutic option using existing antibiotics in combination with broad-spectrum antibiotic adjuvants, to address the prevalent infections caused by MDR Gram-negative pathogens worldwide.
Meirong Song; Yuan Liu; Xiaoyong Huang; Shuangyang Ding; Yang Wang; Jianzhong Shen; Kui Zhu. A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens. Nature Microbiology 2020, 5, 1040 -1050.
AMA StyleMeirong Song, Yuan Liu, Xiaoyong Huang, Shuangyang Ding, Yang Wang, Jianzhong Shen, Kui Zhu. A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens. Nature Microbiology. 2020; 5 (8):1040-1050.
Chicago/Turabian StyleMeirong Song; Yuan Liu; Xiaoyong Huang; Shuangyang Ding; Yang Wang; Jianzhong Shen; Kui Zhu. 2020. "A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens." Nature Microbiology 5, no. 8: 1040-1050.
Yuan Liu; Yuqian Jia; Kangni Yang; Ruichao Li; Xia Xiao; Kui Zhu; Zhiqiang Wang. Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria. Advanced Science 2020, 7, 1 .
AMA StyleYuan Liu, Yuqian Jia, Kangni Yang, Ruichao Li, Xia Xiao, Kui Zhu, Zhiqiang Wang. Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria. Advanced Science. 2020; 7 (12):1.
Chicago/Turabian StyleYuan Liu; Yuqian Jia; Kangni Yang; Ruichao Li; Xia Xiao; Kui Zhu; Zhiqiang Wang. 2020. "Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria." Advanced Science 7, no. 12: 1.
The rapid dissemination of life-threatening multidrug-resistant bacterial pathogens calls for the development of new antibacterial agents and alternative strategies. The virulence factor secreted by bacteria plays a crucial role in the sophisticated processes during infections. Inspired by the unique capacity of many bacteria inducing clotting of plasma to initiate colonization, we propose a programmable antibiotic delivery system for precision therapy using methicillin-resistant S. aureus (MRSA) as a model. Coagulase utilized by MRSA to directly cleave fibrinogen into fibrin, is an ideal target not only for tracking bacterial status but for triggering the collapse of fibrinogen functionalized porous microspheres. Subsequently, staphylokinase, another virulence factor of MRSA, catalyzed hydrolysis of fibrin to further release the encapsulated antibiotics from microspheres. Our sequential triggered-release system exhibits high selectivity to distinguish live or dead MRSA from other pathogenic bacteria. Furthermore, such programmable microspheres clear 99% MRSA in 4 h, and show increased efficiency in a wound healing model in rats. Our study provides a programmable drug delivery system to precisely target bacterial pathogens using their intrinsic enzymatic cascades. This programmable platform with reduced selective stress of antibiotics on microbiota sheds light on the potential therapy for future clinical applications.
Shaoqi Qu; Ying Liu; Qiao Hu; Yiming Han; Zhihui Hao; Jianzhong Shen; Kui Zhu. Programmable antibiotic delivery to combat methicillin-resistant Staphylococcus aureus through precision therapy. Journal of Controlled Release 2020, 321, 710 -717.
AMA StyleShaoqi Qu, Ying Liu, Qiao Hu, Yiming Han, Zhihui Hao, Jianzhong Shen, Kui Zhu. Programmable antibiotic delivery to combat methicillin-resistant Staphylococcus aureus through precision therapy. Journal of Controlled Release. 2020; 321 ():710-717.
Chicago/Turabian StyleShaoqi Qu; Ying Liu; Qiao Hu; Yiming Han; Zhihui Hao; Jianzhong Shen; Kui Zhu. 2020. "Programmable antibiotic delivery to combat methicillin-resistant Staphylococcus aureus through precision therapy." Journal of Controlled Release 321, no. : 710-717.
Background: Klebsiella pneumoniae has been a leading healthcare-acquired infection (HAI) agent worldwide for decades. However, the epidemiological characteristics of K. pneumoniae in lung cancer patients with respiratory infection are unclear. Here, we characterized the frequency of K. pneumoniae in lung cancer patients with respiratory infection in a cancer hospital in China and determined the antibiotic resistance profile, virulence phenotype and clonal relationships among these K. pneumoniae strains. Methods: The clinical data of lung cancer patients with respiratory infection from September 2017 to October 2018 were retrospectively evaluated. Microbiological methods, antimicrobial susceptibility tests, pulsed-field gel electrophoresis (PFGE), polymerase chain reaction (PCR) assays, Sanger sequencing and Galleria mellonella larvae infection model were used in this study. Results: During the study period, a total of 47 lung cancer patients with respiratory infection caused by bacteria were identified, among 27 patients were identified as positive for K. pneumoniae and the positive rate was 57.45%. Among 37 nonduplicate K. pneumoniae strains from these 27 patients, 19 isolates (51.4%) were classified as multidrug resistant (MDR) with high-level resistance to, at least one agent in three or more antibiotic categories, including polymyxin B and tigecycline. Sixteen of the 37 strains (43.2%) were hypermucoviscous isolates. Extended spectrum β-lactamases-producing K. pneumoniae strains consisted of two dominant PFGE types. Furthermore, the assessment of virulence potential using a G. mellonella larvae infection model showed that K. pneumoniae isolated from these patients exhibited a high virulence level. Conclusion: Our data showed that K. pneumoniae is the most critical cause of lung infection in patients with lung cancer in this hospital. The various drug resistance and virulence backgrounds of K. pneumoniae may make this clinical center a breeding ground for superbugs. It is paramount to enhance surveillance of K. pneumoniae strains and take control measures.
Lingchi Ding; Zhiqiang Yang; Junguo Lu; Lichao Ma; Ying Liu; Xiaoyan Wu; Weidong Yao; Xiaodong Zhang; Kui Zhu. Characterization of Phenotypic and Genotypic Traits of Klebsiella pneumoniae from Lung Cancer Patients with Respiratory Infection. Infection and Drug Resistance 2020, ume 13, 237 -245.
AMA StyleLingchi Ding, Zhiqiang Yang, Junguo Lu, Lichao Ma, Ying Liu, Xiaoyan Wu, Weidong Yao, Xiaodong Zhang, Kui Zhu. Characterization of Phenotypic and Genotypic Traits of Klebsiella pneumoniae from Lung Cancer Patients with Respiratory Infection. Infection and Drug Resistance. 2020; ume 13 ():237-245.
Chicago/Turabian StyleLingchi Ding; Zhiqiang Yang; Junguo Lu; Lichao Ma; Ying Liu; Xiaoyan Wu; Weidong Yao; Xiaodong Zhang; Kui Zhu. 2020. "Characterization of Phenotypic and Genotypic Traits of Klebsiella pneumoniae from Lung Cancer Patients with Respiratory Infection." Infection and Drug Resistance ume 13, no. : 237-245.
Pseudomonas aeruginosa is an opportunistic pathogen that often infects open wounds or patients with cystic fibrosis. Once established, P. aeruginosa infections are notoriously difficult to eradicate. This difficulty is in part due to the ability of P. aeruginosa to tolerate antibiotic treatment at the individual-cell level or through collective behaviors. Here, we describe a new phenomenon by which P. aeruginosa tolerates antibiotic treatment. In particular, treatment of P. aeruginosa with sublethal concentrations of antibiotics covering all major classes promoted accumulation of the redox-sensitive phenazine pyocyanin (PYO). PYO in turn conferred general tolerance against diverse antibiotics for both P. aeruginosa and other gram-negative and gram-positive bacteria. This property is shared by other redox-active phenazines produced by P. aeruginosa. Our discovery sheds new insights into the physiological functions of phenazines and has implications for designing effective antibiotic treatment protocols.
Kui Zhu; Shang Chen; Tatyana Sysoeva; Lingchong You. Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa. PLOS Biology 2019, 17, e3000573 .
AMA StyleKui Zhu, Shang Chen, Tatyana Sysoeva, Lingchong You. Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa. PLOS Biology. 2019; 17 (12):e3000573.
Chicago/Turabian StyleKui Zhu; Shang Chen; Tatyana Sysoeva; Lingchong You. 2019. "Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa." PLOS Biology 17, no. 12: e3000573.
The increase in the incidence of antibiotic-resistant Staphylococcus aureus (S. aureus)-associated infections necessitates the urgent development of novel therapeutic strategies and antibacterial drugs. Anti-virulence strategy is an especially compelling alternative strategy due to its low selective pressure for the development of drug resistance in bacteria. Plants and microorganisms are not only important food and medicinal resources, but also serve as sources for the discovery of natural products that target bacterial virulence factors. This review discusses the mechanisms of the major virulence factors of S. aureus, including the accessory gene regulator quorum-sensing system, bacterial biofilm formation, α-hemolysin, sortase A, and staphyloxanthin. We also provide an overview of natural products isolated from plants and microorganisms with activity against the major virulence factors of S. aureus and their adjuvant effects on existing antibiotics to overcome antibiotic-resistant S. aureus. Finally, the limitations of and solutions to these anti-virulence compounds are discussed, which will help in the development of novel antibacterial drugs against antibiotic-resistant S. aureus.
Shuai-Cheng Wu; Fei Liu; Kui Zhu; Jian-Zhong Shen. Natural Products That Target Virulence Factors in Antibiotic-Resistant Staphylococcus aureus. Journal of Agricultural and Food Chemistry 2019, 67, 13195 -13211.
AMA StyleShuai-Cheng Wu, Fei Liu, Kui Zhu, Jian-Zhong Shen. Natural Products That Target Virulence Factors in Antibiotic-Resistant Staphylococcus aureus. Journal of Agricultural and Food Chemistry. 2019; 67 (48):13195-13211.
Chicago/Turabian StyleShuai-Cheng Wu; Fei Liu; Kui Zhu; Jian-Zhong Shen. 2019. "Natural Products That Target Virulence Factors in Antibiotic-Resistant Staphylococcus aureus." Journal of Agricultural and Food Chemistry 67, no. 48: 13195-13211.
Probiotic microbes conferring health benefits to the hosts have attracted great attention. However, the safety of probiotics is not guaranteed, although the increasing widespread use of probiotics with excellent overall safety records. Here, we performed a systematic evaluation of the safety of commercial Bacillus probiotics intended for usage in humans, animals, plants, aquaculture and environment in China. Nearly half of the 65 isolated Bacillus spp. strains from these commercial probiotic products were capable of producing hazardous toxins. Infections with the representative isolates could cause sepsis, intestinal inflammation and liver injury in different mouse models. Additionally, these isolates harbor multiple antimicrobial resistance genes coupled with mobile genetic elements. Collectively, the capability for producing various toxins and harboring mobile antimicrobial resistance genes in Bacillus probiotics indicates a potential risk for One Health.
Yifang Cui; Shaolin Wang; Shuangyang Ding; Jianzhong Shen; Kui Zhu. Toxins and mobile antimicrobial resistance genes in Bacillus probiotics constitute a potential risk for One Health. Journal of Hazardous Materials 2019, 382, 121266 .
AMA StyleYifang Cui, Shaolin Wang, Shuangyang Ding, Jianzhong Shen, Kui Zhu. Toxins and mobile antimicrobial resistance genes in Bacillus probiotics constitute a potential risk for One Health. Journal of Hazardous Materials. 2019; 382 ():121266.
Chicago/Turabian StyleYifang Cui; Shaolin Wang; Shuangyang Ding; Jianzhong Shen; Kui Zhu. 2019. "Toxins and mobile antimicrobial resistance genes in Bacillus probiotics constitute a potential risk for One Health." Journal of Hazardous Materials 382, no. : 121266.