Persistence of commensal multidrug-resistant in the broiler production pyramid is best explained by strain recirculation from the rearing environment.

Despite the success of mitigation policies in several countries to reduce the use of antibiotics in veterinary medicine, pathogenic and commensal bacteria resistant to antibiotics are still circulating in livestock animals. However, factors contributing the most to antimicrobial resistance (AMR) persistence in these settings are yet not clearly identified. The broiler production, with its highly segmented, pyramidal structure offers an ideal context to understand and control the spread of resistant bacteria.

Major primary bile salts repress serovar Typhimurium invasiveness partly via the efflux regulatory locus .

Bile represses serovar Typhimurium (. Typhimurium) intestinal cell invasion, but it remains unclear which bile components and mechanisms are implicated. Previous studies reported that bile inhibits the RamR binding to the promoter, resulting in increased transcription, and that overexpression is associated to decreased expression of type III secretion system 1 (TTSS-1) invasion genes and to impaired intestinal cell invasiveness in .

Crystal structure of the multidrug resistance regulator RamR complexed with bile acids.

During infection, Salmonella senses and responds to harsh environments within the host. Persistence in a bile-rich environment is important for Salmonella to infect the small intestine or gallbladder and the multidrug efflux system AcrAB-TolC is required for bile resistance. The genes encoding this system are mainly regulated by the ramRA locus, which is composed of the divergently transcribed ramA and ramR genes.

Diversity of Escherichia coli strains involved in vertebral osteomyelitis and arthritis in broilers in Brazil.

Background: Locomotor disorders and infections by Escherichia coli represent major concerns to the poultry industry worldwide. Avian pathogenic E. coli (APEC) is associated with extraintestinal infections leading to respiratory or systemic disease known as colibacillosis.

Bile-mediated activation of the acrAB and tolC multidrug efflux genes occurs mainly through transcriptional derepression of ramA in Salmonella enterica serovar Typhimurium.

Objectives: In Salmonella Typhimurium, the genes encoding the AcrAB-TolC multidrug efflux system are mainly regulated by the ramRA locus, composed of the divergently transcribed ramA and ramR genes. The acrAB and tolC genes are transcriptionally activated by RamA, the gene for which is itself transcriptionally repressed by RamR. Previous studies have reported that bile induces acrAB in a ramA-dependent manner, but none provided evidence for an induction of ramA expression by bile.

Lack of efflux mediated quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi A.

Salmonella enterica serovars Typhi and Paratyphi A isolates from human patients in France displaying different levels of resistance to quinolones or fluoroquinolones were studied for resistance mechanisms to these antimicrobial agents. All resistant isolates carried either single or multiple target gene mutations (i.e.

ramR mutations affecting fluoroquinolone susceptibility in epidemic multidrug-resistant Salmonella enterica serovar Kentucky ST198.

A screening for non-target mutations affecting fluoroquinolone susceptibility was conducted in epidemic multidrug-resistant Salmonella enterica serovar Kentucky ST198. Among a panel of representative isolates (n = 27), covering the epidemic, only three showed distinct mutations in ramR resulting in enhanced expression of genes encoding the AcrAB-TolC efflux system and low increase in ciprofloxacin MIC. No mutations were detected in other regulatory regions of this efflux system.

Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses.

Background: Many Gram-positive and Gram-negative bacteria produce large quantities of indole as an intercellular signal in microbial communities. Indole demonstrated to affect gene expression in Escherichia coli as an intra-species signaling molecule. In contrast to E.

Binding of the RamR repressor to wild-type and mutated promoters of the RamA gene involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium.

The transcriptional activator RamA is involved in multidrug resistance (MDR) by increasing expression of the AcrAB-TolC RND-type efflux system in several pathogenic Enterobacteriaceae. In Salmonella enterica serovar Typhimurium (S. Typhimurium), ramA expression is negatively regulated at the local level by RamR, a transcriptional repressor of the TetR family.

ramR mutations involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium.

In the sequenced genome of Salmonella enterica serovar Typhimurium strain LT2, an open reading frame (STM0580) coding for a putative regulatory protein of the TetR family is found upstream of the ramA gene. Overexpression of ramA results in increased expression of the AcrAB efflux pump and, consequently, multidrug resistance (MDR) in several bacterial species. The inactivation of the putative regulatory protein gene upstream of ramA in a susceptible serovar Typhimurium strain resulted in an MDR phenotype with fourfold increases in the MICs of unrelated antibiotics, such as quinolones/fluoroquinolones, phenicols, and tetracycline.

TolC, but not AcrB, is involved in the invasiveness of multidrug-resistant Salmonella enterica serovar Typhimurium by increasing type III secretion system-1 expression.

The AcrAB-TolC efflux system is involved in multidrug and bile salt resistances. In addition, this pump has recently been suggested to increase the invasion of Salmonella enterica serovar Typhimurium (S. Typhimurium) into host cells in vitro and could therefore have an important clinical relevance for multidrug-resistant strains.

Resistance to fluoroquinolones in Salmonella: emerging mechanisms and resistance prevention strategies.

We review the current state of knowledge about the genetic and biochemical mechanisms that mediate quinolone resistance in Salmonella. They include modifications of topoisomerase targets, increased efflux activity and the recently described topoisomerase protection by the plasmid-encoded Qnr protein. We discuss what factors may determine the order of implementation of these various mechanisms in a particular strain, and what strategies could be used to combat resistance, from the inhibition of mutagenesis mechanisms to counteracting, during fluoroquinolone treatment, of resistance mechanisms already set in the infecting strain.

Resistance to fluoroquinolones linked to gyrA and par C mutations and overexpression of acr AB efflux pump in Salmonella enterica serotype Choleraesuis.

Between 2000 and 2002, 60 clinical isolates of Salmonella enterica serotype Choleraesuis were collected to investigate the mechanism of fluoroquinolone resistance. PCR and sequencing were performed to identify mutations in gyrA, gyrB, par C, the Acr AB-TolC efflux pump regulator, acr R, and the global regulons mar RAB and sox RS. All resistant strains showed mutations in the target genes leading to amino acid changes of Ser 83 Phe and Asp 87 Asn in GyrA and Ser 80 Ile in Par C.

TolC but not AcrB is essential for multidrug-resistant Salmonella enterica serotype Typhimurium colonization of chicks.

Objectives: To study the role of the multidrug efflux system AcrAB-TolC in resistance of multidrug-resistant Salmonella enterica serotype Typhimurium (S. Typhimurium) phage type DT104 and DT204 strains to detergents and bile salts. To evaluate the importance of the inner membrane transporter AcrB and the outer membrane component TolC of this efflux system in the colonization of two multidrug-resistant S.

AcrAB-TolC directs efflux-mediated multidrug resistance in Salmonella enterica serovar typhimurium DT104.

Multidrug-resistant Salmonella enterica serovar Typhimurium definitive phage type 104 (DT104) strains harbor a genomic island, called Salmonella genomic island 1 (SGI1), which contains an antibiotic resistance gene cluster conferring resistance to ampicillin, chloramphenicol, florfenicol, streptomycin, sulfonamides, and tetracyclines. They may be additionally resistant to quinolones. Among the antibiotic resistance genes there are two, i.

Plasmid-mediated florfenicol and ceftriaxone resistance encoded by the floR and bla(CMY-2) genes in Salmonella enterica serovars Typhimurium and Newport isolated in the United States.

Multidrug resistance plasmids carrying the bla(CMY-2) gene have been identified in Salmonella enterica serovars Typhimurium and Newport from the United States. This gene confers decreased susceptibility to ceftriaxone, and is most often found in strains with concomitant resistance to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole and tetracycline. The bla(CMY-2)-carrying plasmids studied here were shown to also carry the florfenicol resistance gene, floR, on a genetic structure previously identified in Escherichia coli plasmids in Europe.

Role of TolC and parC mutation in high-level fluoroquinolone resistance in Salmonella enterica serotype Typhimurium DT204.

Objectives: To study the role of TolC and of parC mutation in high-level fluoroquinolone resistance in clonal clinical strains of Salmonella enterica serotype Typhimurium phage type DT204 (S. Typhimurium DT204).

Methods: Deletion of the tolC gene (DeltatolC) was first performed in a susceptible S.

Fitness cost of fluoroquinolone resistance in Salmonella enterica serovar Typhimurium.

High-level fluoroquinolone (FQ) resistance is still infrequent in salmonellae, compared with other pathogenic enterobacteria. Data provided in this work support the hypothesis that the mechanisms that confer high-level FQ resistance on salmonellae have a prohibitive fitness cost and may thus limit the emergence of highly resistant clones. In vitro mutants that were highly resistant to ciprofloxacin (MIC = 8 and 16 micro g ml(-1)) showed generation times 1.

Florfenicol resistance in Salmonella enterica serovar Newport mediated by a plasmid related to R55 from Klebsiella pneumoniae.

Florfenicol resistance has emerged over the past few years in multidrug-resistant Salmonella enterica serovars Typhimurium, Agona and Paratyphi B. The floR gene encoding florfenicol resistance is chromosomally located in these serovars within a genomic island of 43 kb called SGI1 (Salmonella genomic island 1). In the present study, we characterized florfenicol resistance in a strain of S.

The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar typhimurium phage type DT204.

Salmonella enterica serovar Typhimurium phage type DT204 strains isolated from cattle and animal feed in Belgium were characterized for high-level fluoroquinolone resistance mechanisms [MICs to enrofloxacin (Enr) and ciprofloxacin (Cip), 64 and 32 microg/ml, respectively]. These strains isolated during the periods 1991-1994, and in 2000 were clonally related as shown by pulsed-field gel electrophoresis (PFGE). Selected strains studied carried several mutations in the quinolone target genes, i.