Staphylococcus aureus causes a broad range of life-threatening diseases in humans. The pathogenicity of this micro-organism is largely dependent upon its virulence factors. One of the most extensively studied virulence factors is the extracellular protein α-toxin. In this study, we show that allicin, an organosulfur compound, was active against S. aureus with MICs ranged from 32 to 64 μg/mL. Haemolysis, Western blot and real-time RT-PCR assays were used to evaluate the effects of allicin on S. aureus α-toxin production and on the levels of gene expression, respectively. The results of our study indicated that sub-inhibitory concentrations of allicin decreased the production of α-toxin in both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a dose-dependent manner. Furthermore, the transcriptional levels of agr (accessory gene regulator) in S. aureus were inhibited by allicin. Therefore, allicin may be useful in the treatment of α-toxin-producing S. aureus infections.
The present study aimed to evaluate the antimicrobial activity of peppermint oil against Staphylococcus aureus, and further investigate the influence of peppermint oil on S. aureus virulence-related exoprotein production. The data show that peppermint oil, which contained high contents of menthone, isomenthone, neomenthol, menthol, and menthyl acetate, was active against S. aureus with minimal inhibitory concentrations (MICs) ranging from 64-256 µg/mL, and the production of S. aureus exotoxins was decreased by subinhibitory concentrations of peppermint oil in a dose-dependent manner. The findings suggest that peppermint oil may potentially be used to aid in the treatment of S. aureus infections.
Gut dysbiosis contributes to the development and progression of chronic kidney disease (CKD) and its complications. However, the effect of drugs on the gut microbiota of CKD patients and its influence on treatment outcomes remains to be explored. Here, we assessed whether the response of gut microbiota to the traditional Chinese medicine Jian-Pi-Yi-Shen (JPYS) decoction differed from that to piperazine ferulate (PF), a kidney-targeted drug, by 16S rDNA sequencing, and whether the difference could be linked with drug-specific clinical outcomes. We showed that both JPYS and PF improved renal function, but only JPYS was able to restore the blood reticulocyte counting and serum calcium level in CKD rats. We also found that weighted UniFrac beta-diversity of the gut microbiome of the JPYS treated rats was significantly different from that of PF. Microbiome markers of drug-specific response were identified and subjected to correlation network analysis, together with clinical parameters and KEGG pathways. Among the microbiome markers of CKD, Corynebacterium was found to form a network hub that was closely correlated with the JPYS responder Enterococcus, suggesting a potential indirect impact of JPYS on Corynebacterium via interspecies interactions. We also identified two network hubs of the PF responder Blautia and the JPYS-only marker Coprococcus, which were connected with many genera and clinical parameters. They might serve as keystone taxa driving the response of gut microbiota to the drugs and influence host outcomes. Moreover, the JPYS-only marker Clostridium_XIVb was found to be connected to many pathways that are associated with CKD progression and might account for the improved outcomes in the JPYS treated rats. At last, the identified keystone markers of drug response were validated by qPCR for their differential abundance between CKD and the two drugs. Taken together, our study revealed that the responses of gut microbiota to JPYS were distinct from that to PF, and pinpointed drug-specific keystone microbiome markers closely correlated to clinical parameters, which could serve as candidate microbiome targets for further studies on their roles in medicating the drug efficacy of TCM in CKD.
Methicillin-resistant Staphylococcus aureus (MRSA) can spread from animals to humans, but how it adapts to infect both is not fully understood. Our review aimed to determine the prevalence of MRSA in livestock, poultry, and companion animals in different countries, including Bangladesh, the Hong Kong SAR, Mainland China, and Sri Lanka. Articles were collected using PubMed, Embase, Web of Science, Scopus, CINAHL, and Google Scholar. Only prevalence studies that followed the PICO guidelines were included. A random-effects model meta-analysis was used to pool the data. The quality of the evidence and bias were assessed using the GRADEpro and Cochrane collaboration tools. Out of 1438 articles, 69 studies were eligible for meta-analysis. The studies showed significant heterogeneity (I2 = 97.00%, p < 0.0001) in the prevalence of MRSA colonization. Therefore, a random-effects model was used to determine the pooled prevalence of MRSA colonization, which was found to be 4.92% (95% CI: 3.79% to 6.18%). Begg’s test (p = 0.0002) and Egger’s test (p = 0.0044) revealed publication bias. Subgroup analysis of the pooled prevalence of MRSA showed a significant difference (p < 0.00001) when the subgroups were divided by country, MRSA detection method, whether pre-enrichment was performed or not, study period, sample collection location, and study population. Although significant factors can partially explain the heterogeneity, it is crucial to recognize the heterogeneity within different subgroups. The pooled prevalence of MRSA was found to vary significantly (p < 0.00001) among the study periods and has increased since the study period of 2020. Therefore, it is crucial to continuously monitor and implement measures to control the spread of MRSA in animals to minimize the risk of transmission to humans.
The hypervirulent Group B Streptococcus ( Streptococcus agalactiae , GBS) serogroup III clonal cluster 17 has been associated with neonatal GBS invasive disease and meningits. Serogroup III, ST283 has recently been implicated in invasive disease among non-pregnant adults in Asia. These strains cluster with strains from freshwater fishes from aquaculture and a foodborne outbreak of sepsis, especially with septic arthritis, had been linked to such consumption in Singapore in 2015. Through comparative genome analyses of invasive and non-invasive strains of ST283, we identified a truncated response regulator gene in the non-invasive strain. This two component response gene, previously named a DNA binding regulator, is conserved among GBS strains and is a homologue of Bacillus subtilis BceR , the response regulator of the BceRSAB system. Loss of function of the BceR response gene in the invasive GBS strain demonstrated bacitracin susceptibility in ΔBceR mutant with MICs of 256-fold and four-fold reduction in bacitracin and human cathelicin LL-37 compared to wild type and complementation strains. Upregulation of dltA of wild type strain vs ΔBceR mutant was demonstrated ( p <0.0001), and was previously shown in Staphylococcus aureus to resist and repel cationic peptides through excess positive charges with D-alanylation of teichoic acids on the cell wall. In addition, ΔBceR mutant was less susceptible under oxidative stress under H 2 O 2 stress when compared to wild type strain ( p <0.001) and inhibited biofilm formation ( p <0.05 and p < 0.0001 for crystal violet staining and cfu counts). The ΔBceR mutant also showed reduced mortality as compared to wild type strain ( p <0.01) in a murine infection model. Taken together, BceRS is involved in bacitracin and antimicrobial peptide resistance, survival under oxidative stress, biofilm formation and play an important role in the virulence of GBS. Author Summary: Two-component systems (TCSs) play an important role in virulence in bacteria, and are involved in detecting environmental changes. Although S. agalactiae was reported to contain more predicted TCSs than Streptococcus pneumoniae, few have been studied in detail. In this work, comparative genomic analysis of GBS invasive (hyper-virulent) and non-invasive serotype III-4 strains were performed to determine any gene differences that may account for severity of disease in humans. BceR-like TCS was selected and suspected to be involved in virulence, and thus BceR was deleted in a hyper-virulent GBS serotype III-4 strain. We demonstrated that this BceR-like TCS is involved in GBS virulence and induced proinflammatory host immune responses. Our study of TCS BceR may guide further research into the role of other TCSs in GBS pathogenicity, and further explore therapeutic targets for GBS disease.
Population-scale microbiome study poses specific challenges in data analysis, from enterotype analysis, identification of driver species, to microbiome-wide association of host covariates. Application of advanced data mining techniques to high-dimensional complex dataset is expected to meet the rapid advancement in large scale and integrative microbiome research. Here, we present tmap , a topological data analysis framework for population-scale microbiome study. This framework can capture complex shape of large scale microbiome data into a compressive network representation. We also develop network-based statistical analysis for driver species identification and microbiome-wide association analysis. tmap can be used for exploring variations in a population-scale microbiome landscape to study host-microbiome association. Availability and implementation: tmap is available at GitHub ( https://github.com/GPZ-Bioinfo/tmap ), accompanied with online documentation and tutorial ( http://tmap.readthedocs.io ). Contact: http://hk.zhou@siat.ac.cn