The function of the bacterial cytoskeleton in Salmonella pathogenesis

Ac, Doble; Bulmer, David M.; Kharraz, Lubna; Mh, Karavolos; Cm, Khan

doi:10.4161/viru.20993

Cited by 11 publications

(10 citation statements)

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“…Although we did not evaluate the morphological state of the internalized C. jejuni, decreased expression of pgp1 and pgp2 [13,111], two genes contributing to the helical cell shape, suggested that the bacterium lost its curved shape in the vacuole. In the rod shape formation, there is increased expression of penicillin-binding protein genes (pbp) [71,112], supporting our findings as elevated expression levels of pbpA, pbpB, and pbpC in the internalized C. jejuni following 3 h of internalisation were detected ( Supplementary Table S2C). The increased expression levels of the Mre-based cytoskeletal and rod shape determining proteins (MreB, MreC and RodA) strengthen this hypothesis.…”

Section: Discussionsupporting

confidence: 86%

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Virulence Traits of Inpatient Campylobacter jejuni Isolates, and a Transcriptomic Approach to Identify Potential Genes Maintaining Intracellular Survival

et al. 2020

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There are still major gaps in our understanding of the bacterial factors that influence the outcomes of human Campylobacter jejuni infection. The aim of this study was to compare the virulence-associated features of 192 human C. jejuni strains isolated from hospitalized patients with diarrhoea (150/192, 78.1%), bloody diarrhoea (23/192, 11.9%), gastroenteritis (3/192, 1.6%), ulcerative colitis (3/192, 1.5%), and stomach ache (2/192, 1.0%). Traits were analysed with genotypic and phenotypic methods, including PCR and extracellular matrix protein (ECMP) binding, adhesion, and invasion capacities. Results were studied alongside patient symptoms, but no distinct links with them could be determined. Since the capacity of C. jejuni to invade host epithelial cells is one of its most enigmatic attributes, a high throughput transcriptomic analysis was performed in the third hour of internalization with a C. jejuni strain originally isolated from bloody diarrhoea. Characteristic groups of genes were significantly upregulated, outlining a survival strategy of internalized C. jejuni comprising genes related (1) to oxidative stress; (2) to a protective sheath formed by the capsule, LOS, N-, and O-glycosylation systems; (3) to dynamic metabolic activity supported by different translocases and the membrane-integrated component of the flagellar apparatus; and (4) to hitherto unknown genes.

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Section: Discussionsupporting

confidence: 86%

“…All Mre-based bacterial cytoskeleton proteins responsible for the determination of bacterial cell shape, including pbpC (4.455), mreC (2.831), pbpB (2.661), rodA (2.242), and mreB (1.533) [71], increased in the internalized bacterium ( Supplementary Table S2C).…”

Section: Bacterial Gene Expression During Invasionmentioning

confidence: 99%

Virulence Traits of Inpatient Campylobacter jejuni Isolates, and a Transcriptomic Approach to Identify Potential Genes Maintaining Intracellular Survival

et al. 2020

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“…Thus, PBP is also an important target protein for inhibitor development [ 46 ]. These proteins are not only essential for bacterial survival, but also involve in the pathogenesis by interacting with host cytoskeleton [ 47 ]. Hence, targeting this pathway could lead to bacterial lysis by weakening the rigidity and strength of cell wall.…”

Section: Resultsmentioning

confidence: 99%

Target identification in Fusobacterium nucleatum by subtractive genomics approach and enrichment analysis of host-pathogen protein-protein interactions

et al. 2016

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BackgroundFusobacterium nucleatum, a well studied bacterium in periodontal diseases, appendicitis, gingivitis, osteomyelitis and pregnancy complications has recently gained attention due to its association with colorectal cancer (CRC) progression. Treatment with berberine was shown to reverse F. nucleatum-induced CRC progression in mice by balancing the growth of opportunistic pathogens in tumor microenvironment. Intestinal microbiota imbalance and the infections caused by F. nucleatum might be regulated by therapeutic intervention. Hence, we aimed to predict drug target proteins in F. nucleatum, through subtractive genomics approach and host-pathogen protein-protein interactions (HP-PPIs). We also carried out enrichment analysis of host interacting partners to hypothesize the possible mechanisms involved in CRC progression due to F. nucleatum.ResultsIn subtractive genomics approach, the essential, virulence and resistance related proteins were retrieved from RefSeq proteome of F. nucleatum by searching against Database of Essential Genes (DEG), Virulence Factor Database (VFDB) and Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT) tool respectively. A subsequent hierarchical screening to identify non-human homologous, metabolic pathway-independent/pathway-specific and druggable proteins resulted in eight pathway-independent and 27 pathway-specific druggable targets. Co-aggregation of F. nucleatum with host induces proinflammatory gene expression thereby potentiates tumorigenesis. Hence, proteins from IBDsite, a database for inflammatory bowel disease (IBD) research and those involved in colorectal adenocarcinoma as interpreted from The Cancer Genome Atlas (TCGA) were retrieved to predict drug targets based on HP-PPIs with F. nucleatum proteome. Prediction of HP-PPIs exhibited 186 interactions contributed by 103 host and 76 bacterial proteins. Bacterial interacting partners were accounted as putative targets. And enrichment analysis of host interacting partners showed statistically enriched terms that were in positive correlation with CRC, atherosclerosis, cardiovascular, osteoporosis, Alzheimer’s and other diseases.ConclusionSubtractive genomics analysis provided a set of target proteins suggested to be indispensable for survival and pathogenicity of F. nucleatum. These target proteins might be considered for designing potent inhibitors to abrogate F. nucleatum infections. From enrichment analysis, it was hypothesized that F. nucleatum infection might enhance CRC progression by simultaneously regulating multiple signaling cascades which could lead to up-regulation of proinflammatory responses, oncogenes, modulation of host immune defense mechanism and suppression of DNA repair system.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0700-0) contains supplementary material, which is available to authorized users.

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“…The reason for this change is yet to be determined, as this kind of phenotype has not been reported previously for bacteria treated with phenolic acids. Possible explanations for this particular morphology could be related to damage or alterations to proteins more commonly collocated at cellular poles, such as osmotic pressure regulators and division complexes [ 50 ], or could be related to changes in the integrity of bacterial cytoskeletal proteins [ 51 , 52 ]. The morphotype observed for VA was different than the other phenolic acids, as these did not show clear evidence of membrane damage, or cell structure change; however, the overwhelming majority of bacteria observed were found to be mid-division.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial and Antivirulence Impacts of Phenolics on Salmonella Enterica Serovar Typhimurium

et al. 2020

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Salmonella enterica serovar Typhimurium (ST) remains a major infectious agent in the USA, with an increasing antibiotic resistance pattern, which requires the development of novel antimicrobials capable of controlling ST. Polyphenolic compounds found in plant extracts are strong candidates as alternative antimicrobials, particularly phenolic acids such as gallic acid (GA), protocatechuic acid (PA) and vanillic acid (VA). This study evaluates the effectiveness of these compounds in inhibiting ST growth while determining changes to the outer membrane through fluorescent dye uptake and scanning electron microscopy (SEM), in addition to measuring alterations to virulence genes with qRT-PCR. Results showed antimicrobial potential for all compounds, significantly inhibiting the detectable growth of ST. Fluorescent spectrophotometry and microscopy detected an increase in relative fluorescent intensity (RFI) and red-colored bacteria over time, suggesting membrane permeabilization. SEM revealed severe morphological defects at the polar ends of bacteria treated with GA and PA, while VA-treated bacteria were found to be mid-division. Relative gene expression showed significant downregulation in master regulator hilA and invH after GA and PA treatments, while fliC was upregulated in VA. Results suggest that GA, PA and VA have antimicrobial potential that warrants further research into their mechanism of action and the interactions that lead to ST death.

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The function of the bacterial cytoskeleton in Salmonella pathogenesis

Cited by 11 publications

References 0 publications

Virulence Traits of Inpatient Campylobacter jejuni Isolates, and a Transcriptomic Approach to Identify Potential Genes Maintaining Intracellular Survival

Virulence Traits of Inpatient Campylobacter jejuni Isolates, and a Transcriptomic Approach to Identify Potential Genes Maintaining Intracellular Survival

Target identification in Fusobacterium nucleatum by subtractive genomics approach and enrichment analysis of host-pathogen protein-protein interactions

Antimicrobial and Antivirulence Impacts of Phenolics on Salmonella Enterica Serovar Typhimurium

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