Tannic acid, a rich of natural and process-derived phenolic compound, has been shown to be an effective antagonist against viruses and bacteria. In this study, we determined the antimicrobial activity and mechanisms of tannic acid against Staphylococcus aureus with emphasis on inhibiting effect on biofilm formation. Based on the results of time-kill assay, binding ability assay, lysozyme susceptibility assay and the transmission electron microscope, we tentatively speculated that peptidoglycan might be the target of the process that tannic acid destroy the integrity of cell wall, moreover, tannic acid could reduce the biofilm formation at sub-MIC concentrations. These results manifested that natural product tannic acid could serve as a potentially effective candidate for development of novel strategies to treat methicillin-resistant S. aureus infections.

Background: Klebsiella pneumoniae-induced pyogenic liver abscess (KP-PLA) has emerged as a life-threatening disease worldwide. However, to date, a limited number of scholars have attempted to systematically elucidate the characteristics of KP-PLA. The aim of the present study was to analyze clinical, microbiological, and molecular epidemiological characteristics of KP-PLA patients in Southeastern China. Methods: The KP-PLA cases from a tertiary teaching hospital in China from January 2016 to December 2017 were systemically studied and elucidated comprehensively. The virulence factors, resistant spectrum, and clones of K. pneumoniae isolates were identified with string test, polymerase chain reaction (PCR), antimicrobial susceptibility test, and multilocus sequence typing. Moreover, the characteristics in KP-PLA patients with and without other hepatobiliary diseases (OHD) were also been compared. Results: A total of 163 KP-PLA cases were enrolled, in which the majority of those cases were senior males, and often associated with multiple underlying diseases, including diabetes (49.7%). The remaining cases belonged to healthy individuals (50.3%). The clinical symptoms were common but nonspecific, characterized by increased inflammatory parameters and abnormal liver function parameters. The abscess was often right-sided solitary presentation (58.3%). Cephalosporin or carbapenem plus metronidazole combined with percutaneous puncture or catheter drainage were favorable therapeutics. Although low resistance rates of commonly used antimicrobial drugs (< 10%) were observed, twelve strains were identified as multidrug resistant (MDR) strains, and were mainly isolated from the OHD patients. The hypermucoviscosity, as well as K1 and K2 serotypes accounted for 30.7, 40.5, and 19.0%, respectively. Except for iroN (24.5%) and magA (45.4%), the high prevalence of virulence genes (e.g. aerobactin, rmpA, mrkD, fimH, uge, ureA, entB, ybtA, kfuBC, and wcaG) was identified (68.7–100.0%). Additionally, ST23 was found as a predominant sequence type (ST; 38.7%), and three novel STs (ST3507, ST3508 and ST3509) were noted as well. Conclusions: The present study reported the abundant hvKp strains in KP-PLA, as well as convergence of hypervirulent and MDR K. pneumoniae isolates from the KP-PLA patients, particularly those cases with OHD. Given the various clinical manifestations and destructive pathogenicity, determination of the comprehensive characteristics of such isolates is highly essential to effectively carry out for optimal management and treatment of KP-PLA.

Carbapenem-resistant, hypervirulent Klebsiella pneumoniae (CR-hvKP) has recently emerged as a significant threat to public health. In this study, 29 K. pneumoniae isolates were isolated from eight patients admitted to the intensive care unit (ICU) of a comprehensive teaching hospital located in China from March 2017 to January 2018. Clinical information of patients was the basis for the further analyses of the isolates including antimicrobial susceptibility tests, identification of antibiotic resistance and virulence gene determinants, multilocus sequence typing (MLST), XbaI-macrorestriction by pulsed-field gel electrophoresis (PFGE). Selected isolates representing distinct resistance profiles and virulence phenotypes were screened for hypervirulence in a Galleria mellonella larvae infection model. In the course of the outbreak, the overall mortality rate of patients was 100% (n = 8) attributed to complications arising from CR-hvKP infections. All isolates except one (28/29, 96.6%) were resistant to multiple antimicrobial agents, and harbored diverse resistance determinants that included the globally prevalent carbapenemase bla_KPC−2. Most isolates had hypervirulent genotypes being positive for 19 virulence-associated genes, including iutA (25/29, 86.2%), rmpA (27/29, 93.1%), ybtA (27/29, 93.1%), entB (29/29, 100%), fimH (29/29, 100%), and mrkD (29/29, 100%). MLST revealed ST11 for the majority of isolates (26/29, 89,7%). Infection assays demonstrated high mortality in the Galleria mellonella model with the highest LD₅₀ values for three isolates (<10⁵ CFU/mL) demonstrating the degree of hypervirulence of these CR-hvKP isolates, and is discussed relative to previous outbreaks of CR-hvKP.

Background: Bloodstream infection (BSI) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) has been increasingly observed among hospitalized patients. The following study analyzed the epidemiology and microbiological characteristics of MDR-AB, as well as the clinical features, antimicrobial treatments, and outcomes in patients over a six years period in China. Methods: This retrospective study was conducted in a large tertiary hospital in China between January 2013 and December 2018. The clinical and microbiological data of all consecutive hospitalized patients with MDR-AB induced bloodstream infection were included and analyzed. Results: A total of 108 BSI episodes were analyzed. All MDR isolates belonged to ST2, a sequence type that has spread all over the world. Overall, ST2 strains showed strong biofilm formation ability, high serum resistance, and high pathogenicity. As for the clinical characteristics of the patient, 30-day mortality was 69.4% (75/108). The three main risk factors included mechanical ventilation, intensive care unit (ICU) stay, and thrombocytopenia; three protective factors included a change of antimicrobial regimen within 48 h after positive blood culture, use of the antibacterial agent combination, and more inpatient days. The most effective antibacterial regimen was the combination of cefoperazone/sulbactam and tigecycline. Conclusions: BSI caused by ST2 A.baumannii represents a difficult challenge for physicians, considering the high mortality associated with this infection. The combination of cefoperazone/sulbactam and tigecycline may be an effective treatment option.

The goal was to investigate the mechanisms of colistin resistance and heteroresistance in Pseudomonas aeruginosa clinical isolates. Colistin resistance was determined by the broth microdilution method. Colistin heteroresistance was evaluated by population analysis profiling. Time-kill assays were also conducted. PCR sequencing was performed to detect the resistance genes among (hetero)resistant isolates, and quantitative real-time PCR assays were performed to determine their expression levels. Pulsed-field gel electrophoresis and multilocus sequence typing were performed. Lipid A characteristics were determined via matrix-assisted laser desorption–ionization time of flight mass spectrometry (MALDI-TOF MS). Two resistant isolates and 9 heteroresistant isolates were selected in this study. Substitutions in PmrB were detected in 2 resistant isolates. Among heteroresistant isolates, 8 of 9 heteroresistant isolates had nonsynonymous PmrB substitutions, and 2 isolates, including 1 with a PmrB substitution, had PhoQ alterations. Correspondingly, the expression levels of pmrA or phoP were upregulated in PmrB- or PhoQ-substituted isolates. One isolate also found alterations in ParRS and CprRS. The transcript levels of the pmrH gene were observed to increase across all investigated isolates. MALDI-TOF MS showed additional 4-amino-4-deoxy-l-arabinose (l-Ara4N) moieties in lipid A profiles in (hetero)resistant isolates. In conclusion, both colistin resistance and heteroresistance in P. aeruginosa in this study mainly involved alterations of the PmrAB regulatory system. There were strong associations between mutations in specific genetic loci for lipid A synthesis and regulation of modifications to lipid A. The transition of colistin heteroresistance to resistance should be addressed in future clinical surveillance.

Background: The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results: This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions: This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.