Salmonella porins

Cephalosporins are important beta lactam antibiotics, but resistance can be mediated by various mechanisms including production of beta lactamase enzymes, changes in membrane permeability or active efflux. We used an evolution model to study how Salmonella adapts to subinhibitory concentrations of cefotaxime in planktonic and biofilm conditions and characterized the mechanisms underpinning this adaptation. We found that Salmonella rapidly adapts to subinhibitory concentrations of cefotaxime via selection of multiple mutations within the CA-domain region of EnvZ...

The envelope of Gram-negative bacteria is a vital barrier that must balance protection and nutrient uptake. Small RNAs are crucial regulators of the envelope composition and function. Here, using RIL-seq to capture the Hfq-mediated RNA-RNA interactome in Salmonella enterica, we discover envelope-related riboregulators, including OppX. We show that OppX acts as an RNA sponge of MicF sRNA, a prototypical porin repressor. OppX originates from the 5' UTR of oppABCDF, encoding the major inner-membrane oligopeptide transporter, and sequesters MicF's seed region to derepress the synthesis of the porin OmpF...

Cointegrate/hybrid plasmids combine the genetic elements of two or more plasmids and generally carry abundant antimicrobial resistance determinants. Hence, the spread of cointegrate plasmids will accelerate the transmission of AMR genes. To evaluate the transmission risk caused by cointegrate plasmids, we investigated the structural diversity, fitness cost, and stability of a cointegrate plasmid in Klebsiella pneumoniae YZ6 and Escherichia coli EC600. The cointegrate plasmid pSL131_IncA/C_IncX3 was from a clinical Salmonella Lomita strain...

OBJECTIVES: Salmonella is one of the most important genera of enteric pathogenic bacteria that threatened duck farms. The aim of this study was to increase the understanding of antimicrobial resistance mechanisms in duck-origin S. enterica serovar Indiana isolate. METHODS: Salmonella was isolated from duck cloacal swabs collected from the duck farms located in Zhejiang and Henan province of China. All of the isolates were identified after a series of confirmation tests including selective culture method, biochemical tests, serotyping and PCR targeting invA gene, and then subjected to antimicrobial susceptibility testing using the standard Kirby-Bauer disk diffusion method...

The evolution of resistance in Salmonella to fluoroquinolones (FQs) under a broad range of sub-inhibitory concentrations (sub-MICs) has not been systematically studied. This study investigated the mechanism of resistance development in Salmonella enterica serovar Enteritidis ( S . Enteritidis) under sub-MICs of 1/128×MIC to 1/2×MIC of enrofloxacin (ENR), a widely used veterinary FQ. It was shown that the resistance rate and resistance level of S . Enteritidis varied with the increase in ENR concentration and duration of selection...

Salmonella enterica serovar Typhi ( S . Typhi) porins, OmpC and OmpF, are potent inducers of the immune response against S . Typhi in mice and humans. Vaccination with porins induces the protection against 500 LD50 of S . Typhi, life-lasting bactericidal antibodies and effector T cell responses in mice; however, the nature of the memory T cell compartment and its contribution to protection remains unknown. In this work, we firstly observed that vaccination with porins induces in situ (skin) CD4+ and CD8+ T cell responses...

The CRISPR-Cas cluster is found in many prokaryotic genomes including those of the Enterobacteriaceae family. Salmonella enterica serovar Typhi ( S . Typhi) harbors a Type I-E CRISPR-Cas locus composed of cas3 , cse1 , cse2 , cas7 , cas5 , cas6e , cas1 , cas2 , and a CRISPR1 array. In this work, it was determined that, in the absence of cas5 or cas2 , the amount of the OmpC porin decreased substantially, whereas in individual cse2 , cas6e , cas1 , or cas3 null mutants, the OmpF porin was not observed in an electrophoretic profile of outer membrane proteins...

The Yersinia bacteriophages fPS-2, fPS-65, and fPS-90, isolated from pig stools, have long contractile tails and elongated heads, and they belong to genus Tequatroviruses in the order Caudovirales . The phages exhibited relatively wide host ranges among Yersinia pseudotuberculosis and related species. One-step growth curve experiments revealed that the phages have latent periods of 50-80 min with burst sizes of 44-65 virions per infected cell. The phage genomes consist of circularly permuted dsDNA of 169,060, 167,058, and 167,132 bp in size, respectively, with a G + C content 35...

Immunotherapy has improved the clinical response in melanoma patients, although a relevant percentage of patients still cannot be salvaged. The search for the immune populations that provide the best tumor control and that can be coaxed by immunotherapy strategies is a hot topic in cancer research nowadays. Tumor-infiltrating TCF-1+ progenitor exhausted CD8+ T cells seem to grant the best melanoma prognosis and also efficiently respond to anti-PD-1 immunotherapy, giving rise to a TIM-3+ terminally exhausted population with heightened effector activity...

The development of nanotechnology in the last two decades has led to the use of silver nanoparticles (AgNPs) in various biomedical applications, including antimicrobial, anti-inflammatory, and anticancer therapies. However, the potential of the medical application of AgNPs depends on the safety of their use. In this work, we assessed the in vitro cytotoxicity and genotoxicity of silver nanoparticles and identified biomolecules covering AgNPs synthesized from actinobacterial strain SH11. The cytotoxicity of AgNPs against MCF-7 human breast cancer cell line and murine macrophage cell line RAW 264...

Salmonella developed drug-resistance under durative antibiotic pressures pressure. The widespread prevalence of Salmonella has been associated with not only drug-resistance but also pathogenicity. Outer membrane porin proteins (OMPs) are critical for the drug resistance of bacteria. Virulence genes in Salmonella pathogenicity islands (SPIs) play key roles in the virulence of bacteria. In this study, we analyzed the expression levels of three critical genes in ciprofloxacin-resistant strains and ciprofloxacin-susceptible strains of Salmonella, including outer membrane porin protein F (ompF), virulence genes invA and invE...

Lipopolysaccharide (LPS) O-antigen (O-Ag) is known to limit antibody binding to surface antigens, although the relationship between antibody, O-Ag and other outer-membrane antigens is poorly understood. Here we report, immunization with the trimeric porin OmpD from Salmonella Typhimurium (STmOmpD) protects against infection. Atomistic molecular dynamics simulations indicate this is because OmpD trimers generate footprints within the O-Ag layer sufficiently sized for a single IgG Fab to access. While STmOmpD differs from its orthologue in S...

In order to improve the immunogenicity of the highly purified vaccine antigens, addition of an adjuvant to formulation, without affecting the safety of the vaccine, has been the key aim of the vaccine formulators. In recent years, adjuvants which are composed of a delivery system and immunopotentiators have been preferred to induce potent immune responses. In this study, we have combined Salmonella Typhi porins and chitosan to develop a new adjuvant system to enhance the immunogenicity of the highly purified antigens...

Four clinical isolates of Salmonella Enteritidis, susceptible to ciprofloxacin, and their spontaneous ciprofloxacin resistant (MICs from 8 to 16 μg/mL) and highly resistant (MIC 2048 μg/mL) mutants were used to gain an insight into the dynamics of development of fluoroquinolone (FQs) resistance in S. Enteritidis serovar. The first two high-frequency (i.e., mutations that occurred in each tested strain) mutations occurred in the gyrA , resulting in amino acid substitutions S83Y and S83F as well as D87G. Amino acid substitution D87G was significantly associated with the highly resistant mutants...

Bacterial cold shock proteins (CSPs) function as RNA chaperones. To assess CSP's roles in the intracellular human pathogen, Salmonella Typhimurium, we analyzed their expression in varied stress conditions. We found that cold shock protein E ( cspE   or STM14_0732) is up-regulated during bile salt-induced stress and that an S Typhimurium strain lacking cspE (Δ cspE ) displays dose-dependent sensitivity to bile salts, specifically to deoxycholate. We also found that an uncharacterized gene, yciF (STM14_2092) is up-regulated in response to bile stress in WT, but not in the Δ cspE strain...

The aim of this study was to determine whether sub-lethal concentrations of ceftriaxone could alter antibiotic resistance patterns in Salmonella strains. Three multiple antibiotic-resistant Salmonella isolates and the control strain ATCC 13076 were subjected to induction experiments by stepwise increases in sub-lethal concentrations of ceftriaxone. Sub-lethal levels of ceftriaxone induced antibiotic-resistance but not control Salmonella isolates to ceftriaxone and to other antibiotics. After 100 generations in two months when the antibiotic stress was removed, only one isolate (S...

The lack of efficacy of current antibacterials to treat multidrug resistant bacteria poses a life-threatening alarm. In order to develop enhancers of the antibacterial activity, we carried out a medicinal chemistry campaign aiming to develop inhibitors of enzymes that synthesise cysteine and belong to the reductive sulphur assimilation pathway, absent in mammals. Previous studies have provided a novel series of inhibitors for O-acetylsulfhydrylase - a key enzyme involved in cysteine biosynthesis. Despite displaying nanomolar affinity, the most active representative of the series was not able to interfere with bacterial growth, likely due to poor permeability...

Salmonella enterica serovar Typhimurium (S. typhimurium) can cause food- and water-borne illness with diverse clinical manifestations. One key factor for S. typhimurium pathogenesis is the alternative sigma factor σE , which is encoded by the rpoE gene and controls the transcription of genes required for outer-membrane integrity in response to alterations in the bacterial envelope. The canonical pathway for σE activation involves proteolysis of the antisigma factor RseA, which is triggered by unfolded outer-membrane porins (OMPs) and lipopolysaccharides (LPS) that have accumulated in the periplasm...

This study was designed to evaluate the resistance phenotype and genotype of wild type (WT)-, cefotaxime (CET)-, and ciprofloxacin (CIP)-induced Salmonella Typhimurium ATCC 19585, CIP-resistant Salmonella Typhimurium ATCC 19585, Salmonella Typhimurium CCARM 8009, and Salmonella Typhimurium KCCM 40253 before and after exposure to pH 4.5, 4% NaCl, and heat at 42°C. The susceptibilities of WT Salmonella Typhimurium ATCC 19585 and WT Salmonella Typhimurium KCCM 40253 to all antibiotics tested in this study were decreased after CET and CIP induction with the exception with kanamycin, meropenem, and polymyxin B...

Non-typhoidal serovars of Salmonella enterica (NTS) are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical "last resort" antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae , Escherichia coli , and Enterobacter , which are major nosocomial pathogens affecting debilitated and immunocompromised patients), carbapenem resistance is still very rare in NTS...