Project description:Streptococcus pyogenes (Group A Streptococcus: GAS) is a major human pathogen that causes streptococcal pharyngitis, skin and soft-tissue infections, and life-threatening conditions such as streptococcal toxic shock syndrome (STSS). A large number of virulence-related genes are encoded on GAS genomes, which are involved in host-pathogen interaction, colonization, immune invasion, and long-term survival within hosts, causing the diverse symptoms. Here, we investigated the interaction between GAS-derived extracellular vesicles and host cells in order to reveal pathogenicity mechanisms induced by GAS infection.
Project description:Streptococcus suis is a major pig pathogen as well as an emerging zoonotic pathogen. We studied the generic and adaptive resistance response of S. suis upon exposure to sub-lethal concentrations of the human cathelicidin LL-37. We aimed to search for inducible mechanisms of resistance to AMPs as well as induction of virulence gene expression upon exposure to AMPs, in order to gain insights into host-derived factors that might mediate S. suis pathogenesis.
Project description:Streptococcus suis is an important emerging worldwide pig pathogen and zoonotic agent with rapid evolution of virulence and drug resistance. Licochalcone A, used in traditional Chinese medicine, exhibits antimicrobial, antioxidant and anti-inflammatory activities. Herein, a whole-genome DNA microarray was used to investigate the global transcriptional regulation of Streptococcus suis 05ZYH33 treated by subinhibitory concentration of licochalcone A. 132 genes were differentially regulated upon liochalcone A treatment, including 78 genes up-regulated and 54 genes down-regulated which included many central biological functions such as metabolism, transcription and translation. We tried to investigate the antimicrobial mechanism of licochalcone A in the aspect of bacterial cell cycle control. Our analysis indicated that licochalcone A might inhibit the growth of S. suis by controlling the replication initiation and cell division through amino acid metabolism.
Project description:Antibiotic use can lead to expansion of multi-drug resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank that enables the rapid design of antimicrobial bacteriophage cocktails to treat multi-drug resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identified host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank and experimental evolution strategies, we formulated combinations of phages that minimize the occurrence of phage resistance in vitro. Optimized bacteriophage cocktails selectively suppressed the burden of multi-drug resistant K. pneumoniae in the mouse gut microbiome and drove bacterial populations to lose key virulence factors that act as phage receptors. Further, phage-mediated diversification of bacterial populations in the gut enabled co-evolution of phage variants with higher virulence and a broader host range. Altogether, the Klebsiella PhageBank represents a roadmap for both phage researchers and clinicians to enable phage therapy against a critical multidrug-resistant human pathogen.
Project description:Shotgun metagenomic sequencing data for nasopharyngeal colonization dynamics with Streptococcus pneumoniae and associated antimicrobial-resistance in a South African birth cohort.
Project description:Two-component regulatory systems (TCS) are one of the most widespread mechanism that bacteria use to sense and respond to environmental changes. In Streptococcus pneumoniae, a total of 13 TCS and one orphan response regulator have been identified and many of them have been linked to pathogenicity. Notably, TCS01 strongly contributed to pneumococcal virulence in several infection models. However, it remains one of the least studied TCS in pneumococci and its functional role is still unclear. In this study, we demonstrate that TCS01 upregulates a BceAB-type ATP-Binding Cassette (ABC) transporter that mediates resistance to several antimicrobial peptides targeting lipid II. Even though Tcs01 and BceAB genes are localized far apart from each other in the genome, disruption of either of them equally sensitized the bacterium to the same antimicrobial peptides. Although it is still poorly understood how S. pneumoniae can switch from a harmless colonizer of the human nasopharynx to a serious pathogen causing a variety of diseases, TCS01 likely contributes to the physiopathology of this organism by cooperating with a BceAB-type transporter to sense and induce resistance to antimicrobial peptides encountered in the human host.
Project description:Streptococcus suis is an important emerging worldwide pig pathogen and zoonotic agent with rapid evolution of virulence and drug resistance. Licochalcone A, used in traditional Chinese medicine, exhibits antimicrobial, antioxidant and anti-inflammatory activities. Herein, a whole-genome DNA microarray was used to investigate the global transcriptional regulation of Streptococcus suis 05ZYH33 treated by subinhibitory concentration of licochalcone A. 132 genes were differentially regulated upon liochalcone A treatment, including 78 genes up-regulated and 54 genes down-regulated which included many central biological functions such as metabolism, transcription and translation. We tried to investigate the antimicrobial mechanism of licochalcone A in the aspect of bacterial cell cycle control. Our analysis indicated that licochalcone A might inhibit the growth of S. suis by controlling the replication initiation and cell division through amino acid metabolism. A cDNA microarray imprinted with 2156 genes representing about 98% of Streptococcus suis serotype 2 genome was used for transcriptome analysis. For two-sample (reference vs. test) microarray hybridization, four independent bacterial cultures from each condition were prepared as biological replicates for RNA isolation. Four dual-fluorescence-labeled cDNA probes were prepared to hybridize with four slides, respectively. Pairwise comparisons were made using dye swaps to avoid labeling bias. A ratio of mRNA levels (test/reference) was calculated for each gene. Significant changes of gene expression were identified with the SAM software. After the SAM analysis, only genes with at least 2-fold changes in expression were collected for further analysis.
Project description:Pseudomonas aeruginosa is a re-emerging opportunistic pathogen with broad antimicrobial resistance. We have previously reported that the major siderophore pyoverdine from this pathogen disrupts mitochondrial networks and induces a lethal hypoxic response in model host Caernorhabditis elegans. However, the mechanism of such cytotoxicity remained unclear. Here, we demonstrate that pyoverdine translocates into host cells, binding to host ferric iron sources. The reduction of host iron content disrupts mitochondrial function such as NADH oxidation and ATP production and activates mitophagy. This activates a specific immune response that is distinct from colonization-based pathogensis and exposure to downstream pyoverdine effector Exotoxin A. Host response to pyoverdine resembles that of a hypoxic crisis or iron chelator treatment. Furthermore, we demonstrate that pyoverdine is a crucial virulence factor in P. aerguinosa pathogenesis against cystic fibrosis patients; ΔF508 mutation in human CFTR increases susceptibility to pyoverdine-mediated damage.
Project description:The zig-zag model of host-pathogen interaction describes the relative strength of defense response across a spectrum of pathogen-induced plant phenotypes. A stronger defense response results in increased resistance. Here, we investigate the strength of pathogen virulence during disease and place these findings in the context of the zig-zag model. Xanthomonas vasicola pv. holcicola (Xvh) causes sorghum bacterial leaf streak. Despite being widespread, this disease has not been described in detail at the molecular level. We divided diverse sorghum genotypes into three groups based on disease symptoms: water-soaked lesions, red lesions, and resistance. Bacterial growth assays confirmed that these three phenotypes represent a range of resistance and susceptibility. To simultaneously reveal defense and virulence responses across the spectrum of disease phenotypes, we performed dual RNA-seq on Xvh-infected sorghum. Consistent with the zig-zag model, the expression of plant defense-related genes was strongest in the resistance interaction. Surprisingly, bacterial virulence genes related to the type III secretion system (T3SS) and type III effectors (T3Es) were also most highly expressed in the resistance interaction. This expression pattern was observed at multiple time points within the sorghum-Xvh pathosystem. Further, a similar expression pattern was observed in Arabidopsis infected with Pseudomonas syringae for effector-triggered immunity via AvrRps4 but not AvrRpt2. Specific metabolites were able to repress the Xvh virulence response in vitro and in planta suggesting a possible signaling mechanism. Taken together, these findings reveal multiple permutations of the continually evolving host-pathogen arms race from the perspective of host defense and pathogen virulence responses.
Project description:Transcriptomic profiling was done on barley samples incoulated with different Puccinia graminis f. sp. tritici (Pgt) isolates of varying virulence profile on barley stem rust resistance gene rpg4/5 and Rpg1. Several differentally expressed host and pathogen genes were identified while comparing gene expression profiles between group of samples inoculated with isoaltes of varying virulence. Several variants with genes of pathogen were idnetified that are possibly associated with virulence to rpg4/5.