Salmonella enterica Serovar Typhimurium Exploits Inflammation to Modify Swine Intestinal Microbiota

Salmonella enterica serovar Typhimurium is an important zoonotic gastrointestinal pathogen responsible for foodborne disease worldwide. It is a successful enteric pathogen because it has developed virulence strategies allowing it to survive in a highly inflamed intestinal environment exploiting inflammation to overcome colonization resistance provided by intestinal microbiota. In this study, we used piglets featuring an intact microbiota, which naturally develop gastroenteritis, as model for salmonellosis. We compared the effects on the intestinal microbiota induced by a wild type and an attenuated S. Typhimurium in order to evaluate whether the modifications are correlated with the virulence of the strain. This study showed that Salmonella alters microbiota in a virulence-dependent manner. We found that the wild type S. Typhimurium induced inflammation and a reduction of specific protecting microbiota species (SCFA-producing bacteria) normally involved in providing a barrier against pathogens. Both these effects could contribute to impair colonization resistance, increasing the host susceptibility to wild type S. Typhimurium colonization. In contrast, the attenuated S. Typhimurium, which is characterized by a reduced ability to colonize the intestine, and by a very mild inflammatory response, was unable to successfully sustain competition with the microbiota.

Association of extended-spectrum β-lactamase VEB-5 and 16S rRNA methyltransferase armA in Salmonella enterica from the United Kingdom

Aminoglycosides and beta-lactams are used for the treatment of a wide range of infections due to both Gram-negative and Gram-positive. An emerging aminoglycoside resistance mechanism, methylation of the aminoacyl site of the 16S rRNA, confers high-level resistance to clinically important aminoglycosides such as amikacin, tobramycin and gentamicin. Eight 16S rRNA methyltransferase genes, armA, rmtA, rmtB, rmtC, rmtD, rmtE, rmtF and npmA, have been identified in several species of enterobacteria worldwide (2, 6, 7, 9, 11, 13, 14). Resistance to extended spectrum β-lactams remains additionally an important clinical problem. Apart from the large TEM, SHV, and CTX-M families, several other extended-spectrum β-lactamases (ESBLs) have been identified, including VEB enzymes, which confer high-level resistance to cephalosporins and monobactams. Although 16S rRNA methyltransferases have been frequently identified associated with different ESBLs, there has been no report of association of a 16S rRNA methyltransferase with a VEB enzyme, except for the identification of rmtC with blaVEB-6 (14)

ArmA methyltransferase in a monophasic Salmonella enterica isolate from food

The 16S rRNA methyltransferase ArmA is a worldwide emerging determinant that confers high-level resistance to most clinically relevant aminoglycosides. We report here the identification and characterization of a multidrug-resistant Salmonella enterica subspecies I.4,12:i:- isolate recovered from chicken meat sampled in a supermarket on February 2009 in La Reunion, a French island in the Indian Ocean. Susceptibility testing showed an unusually high-level resistance to gentamicin, as well as to ampicillin, expanded-spectrum cephalosporins and amoxicillin-clavulanate. Molecular analysis of the 16S rRNA methyltransferases revealed presence of the armA gene, together with bla(TEM-1), bla(CMY-2), and bla(CTX-M-3). All of these genes could be transferred en bloc through conjugation into Escherichia coli at a frequency of 10(-5) CFU/donor. Replicon typing and S1 pulsed-field gel electrophoresis revealed that the armA gene was borne on an ~150-kb broad-host-range IncP plasmid, pB1010. To elucidate how armA had integrated in pB1010, a PCR mapping strategy was developed for Tn1548, the genetic platform for armA. The gene was embedded in a Tn1548-like structure, albeit with a deletion of the macrolide resistance genes, and an IS26 was inserted within the mel gene. To our knowledge, this is the first report of ArmA methyltransferase in food, showing a novel route of transmission for this resistance determinant. Further surveillance in food-borne bacteria will be crucial to determine the role of food in the spread of 16S rRNA methyltransferase genes worldwide.

Multiresistant Salmonella enterica serovar 4,[5],12:i:- in Europe: a new pandemic strain?

A marked increase in the prevalence of S. enterica serovar 4,[5],12:i:- with resistance to ampicillin, streptomycin, sulphonamides and tetracyclines (R-type ASSuT) has been noted in food-borne infections and in pigs/pig meat in several European countries in the last ten years. One hundred and sixteen strains of S. enterica serovar 4,[5],12:i:- from humans, pigs and pig meat isolated in England and Wales, France, Germany, Italy, Poland, Spain and the Netherlands were further subtyped by phage typing, pulsed-field gel electrophoresis and multilocus variable number tandem repeat analysis to investigate the genetic relationship among strains. PCR was performed to identify the fljB flagellar gene and the genes encoding resistance to ampicillin, streptomycin, sulphonamides and tetracyclines. Class 1 and 2 integrase genes were also sought. Results indicate that genetically related serovar 4,[5],12:i:- strains of definitive phage types DT193 and DT120 with ampicillin, streptomycin, sulphonamide and tetracycline resistance encoded by blaTEM, strA-strB, sul2 and tet(B) have emerged in several European countries, with pigs the likely reservoir of infection. Control measures are urgently needed to reduce spread of infection to humans via the food chain and thereby prevent the possible pandemic spread of serovar 4,[5],12:i:- of R-type ASSuT as occurred with S. Typhimurium DT104 during the 1990s.