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1.
Arch Microbiol ; 206(7): 302, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874634

RESUMO

Host-generated antimicrobial peptides (AMPs) play a pivotal role in defense against bacterial pathogens. AMPs kill invading bacteria majorly by disrupting the bacterial cell walls. AMPs are actively synthesized and released into the lumen of the gastrointestinal tract to limit colonization of enteric pathogens like Salmonella typhimurium (S. typhimurium). However, S. typhimurium has evolved several resistance mechanisms to defend AMPs. The multicomponent SapABCDF uptake transporter is one such system that helps in resisting AMPs. In the current study, we analyzed the role of S. typhimurium SapA against stress survival and virulence of this bacterium. ∆sapA mutant strain showed hypersensitivity to AMPs, like melittin and mastoparan. Further, ∆sapA mutant showed more than 22 folds (p = 0.019) hypersensitivity to neutrophils as compared to the WT strain of S. typhimurium. In addition, ∆sapA strain showed defective survival in mice. In conclusion, the results of the current study suggest that the SapA is essential for survival against AMPs and virulence of S. typhimurium.


Assuntos
Neutrófilos , Salmonella typhimurium , Animais , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/patogenicidade , Salmonella typhimurium/genética , Camundongos , Neutrófilos/imunologia , Neutrófilos/microbiologia , Virulência , Peptídeos Antimicrobianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Feminino , Camundongos Endogâmicos BALB C , Infecções por Salmonella/microbiologia , Peptídeos Catiônicos Antimicrobianos/farmacologia
2.
Mol Biol Rep ; 51(1): 404, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456953

RESUMO

BACKGROUND: Pathogenic and non-pathogenic strains of Escherichia coli harbouring antibiotic resistance genes (ARGs) from any source (clinical samples, animal settings, or environment) might be transmitted and contribute to the spread and increase of antibiotic resistance in the biosphere. The goal of this study was to investigate the genome to decipher the repertoire of ARGs, virulence genes carried by E. coli strains isolated from livestock, poultry, and their handlers (humans), and then unveil the genetic relatedness between the strains. METHODS: Whole genome sequencing was done to investigate the genetic makeup of E. coli isolates (n = 20) [swine (n = 2), cattle (n = 2), sheep (n = 4), poultry (n = 7), and animal handlers (n = 5)] from southern India. The detection of resistome, virulome, biofilm forming genes, mobile genetic elements (MGE), followed by multilocus sequence typing (MLST) and phylogenetic analyses, were performed. RESULTS: E. coli strains were found to be multi drug resistant, with a resistome encompassing > 20 ARGs, the virulome-17-22 genes, and > 20 key biofilm genes. MGE analysis showed four E. coli isolates (host: poultry, swine and cattle) harbouring composite transposons with ARGs/virulence genes (blaTEM, dfr, qnr/nleB, tir, eae,and esp) with the potential for horizontal transfer. MLST analyses revealed the presence of ST937 and ST3107 in both livestock/poultry and their handlers. Phylogenomic analyses with global E. coli isolates (human/livestock/poultry hosts) showed close relatedness with strains originating from different parts of the world (the United States, China, etc.). CONCLUSION: The current study emphasizes the circulation of strains of pathogenic sequence types of clinical importance, carrying a diverse repertoire of genes associated with antibiotic resistance, biofilm formation and virulence properties in animal settings, necessitating immediate mitigation measures to reduce the risk of spread across the biosphere.


Assuntos
Infecções por Escherichia coli , Saúde Única , Animais , Bovinos , Humanos , Suínos , Ovinos/genética , Escherichia coli , Aves Domésticas/genética , Filogenia , Virulência/genética , Gado/genética , Infecções por Escherichia coli/veterinária , Tipagem de Sequências Multilocus , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos
3.
Free Radic Biol Med ; 213: 322-326, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38262547

RESUMO

Sulphur containing amino acids, methionine and cysteine are highly prone to oxidation. Reduction of oxidized methionine (Met-SO) residues to methionine (Met) by methionine sulfoxide reductases (Msrs) enhances the survival of bacterial pathogens under oxidative stress conditions. S. Typhimurium encodes two types (cytoplasmic and periplasmic) of Msrs. Periplasmic proteins, due to their location are highly vulnerable to host-generated oxidants. Therefore, the periplasmic Msr (MsrP) mediated repair (as compared to the cytoplasmic counterpart) might play a more imperative role in defending host-generated oxidants. Contrary to this, we show that in comparison to the ΔmsrP strain, the mutant strains in the cytoplasmic Msrs (ΔmsrA and ΔmsrAC strains) showed many folds more susceptibility to chloramine-T and neutrophils. Further ΔmsrA and ΔmsrAC strains accumulated higher levels of ROS and showed compromised fitness in mice spleen and liver. Our data suggest the pivotal role of cytoplasmic Msrs in oxidative stress survival of S. Typhimurium.


Assuntos
Estresse Oxidativo , Salmonella typhimurium , Animais , Camundongos , Salmonella typhimurium/genética , Virulência , Metionina Sulfóxido Redutases/genética , Metionina Sulfóxido Redutases/metabolismo , Oxirredução , Oxidantes , Metionina/metabolismo , Racemetionina/metabolismo
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