Kingsley, R.A. et al. Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome Res. 19, 2279-2287

The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Cambridge, United Kingdom.
Genome Research (Impact Factor: 14.63). 11/2009; 19(12):2279-87. DOI: 10.1101/gr.091017.109
Source: PubMed


Whereas most nontyphoidal Salmonella (NTS) are associated with gastroenteritis, there has been a dramatic increase in reports of NTS-associated invasive disease in sub-Saharan Africa. Salmonella enterica serovar Typhimurium isolates are responsible for a significant proportion of the reported invasive NTS in this region. Multilocus sequence analysis of invasive S. Typhimurium from Malawi and Kenya identified a dominant type, designated ST313, which currently is rarely reported outside of Africa. Whole-genome sequencing of a multiple drug resistant (MDR) ST313 NTS isolate, D23580, identified a distinct prophage repertoire and a composite genetic element encoding MDR genes located on a virulence-associated plasmid. Further, there was evidence of genome degradation, including pseudogene formation and chromosomal deletions, when compared with other S. Typhimurium genome sequences. Some of this genome degradation involved genes previously implicated in virulence of S. Typhimurium or genes for which the orthologs in S. Typhi are either pseudogenes or are absent. Genome analysis of other epidemic ST313 isolates from Malawi and Kenya provided evidence for microevolution and clonal replacement in the field.

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    • "The BTP1 prophage is one of the distinguishing genetic features of the iNTS S. Typhimurium strain D23580 (Kingsley et al., 2009). Previously, a Salmonella-wide genome analysis for the occurrence of O-antigen modifying gtr operons determined that this prophage encoded an uncharacterized gtr operon (Davies et al., 2013). "
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    ABSTRACT: Salmonella Typhimurium isolate D23580 represents a recently identified ST313 lineage of invasive non-Typhoidal Salmonellae (iNTS). One of the differences between this lineage and other non-iNTS S. Typhimurium isolates is the presence of prophage BTP1. This prophage encodes a gtrC gene, implicated in O-antigen modification. GtrC(BTP1) is essential for maintaining O-antigen length in isolate D23580, since a gtr(BTP1) mutant yields a short O-antigen. This phenotype can be complemented by gtrC(BTP1) or very closely related gtrC genes. The short O-antigen of the gtr(BTP1) mutant was also compensated by deletion of the BTP1 phage tailspike gene in the D23580 chromosome. This tailspike protein has a putative endorhamnosidase domain and thus may mediate O-antigen cleavage. Expression of the gtrC(BTP1) gene is, in contrast to expression of many other gtr operons, not subject to phase variation and transcriptional analysis suggests that gtrC is produced under a variety of conditions. Additionally, GtrC(BTP1) expression is necessary and sufficient to provide protection against BTP1 phage infection of an otherwise susceptible strain. These data are consistent with a model in which GtrC(BTP1) mediates modification of the BTP1 phage O-antigen receptor in lysogenic D23580, and thereby prevents superinfection by itself and other phage that use the same O-antigen co-receptor. This article is protected by copyright. All rights reserved.
    Molecular Microbiology 01/2015; 96(2). DOI:10.1111/mmi.12933 · 4.42 Impact Factor
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    • "In addition, S. Typhimurium isolates of animal origin were shown to be resistant to several drugs including ceftiofur and ciprofloxacin [56-61]. Furthermore, MDR genes located on a virulence-associated plasmid of S. Typhimurium were identified [62] and ST313 appears to have occupied a niche provided by HIV, malaria, and malnutrition in SSA [63]. "
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    ABSTRACT: Background Antimicrobial resistant Salmonella is a global problem and recently, a strain on the verge of pan-resistance was reported. In Ethiopia, the therapeutic management of Salmonellosis is difficult because drug sensitivity tests are not routinely carried out and treatment alternatives are not available in most health care facilities. The objectives of this study were to estimate the temporal changes and proportions of drug resistant isolates in Ethiopia. Methods Published studies on drug resistant Salmonella isolates were searched in Medline, Google Scholar and the lists of references of articles. Eligible studies were selected by using inclusion and exclusion criteria. Generic, methodological and statistical information were extracted from the eligible studies. The extracted data included the proportions of ampicillin, co-trimoxazole, chloramphenicol, ceftriaxone, ciprofloxacin and multi-drug resistant isolates. Pooled proportions were estimated by a random effects model. Results The odds of multi-drug resistant isolates in the 2000s was higher than before the 1990s (OR =18.86, 95% CI = 13.08, 27.19). The pooled proportions of ampicillin, co-trimoxazole, chloramphenicol, ciprofloxacin and multi-drug resistant isolates in the 2000s were 86.01%, 68.01%, 62.08%, 3.61% and 79.56% respectively. S. Concord (>97%) was resistant to ampicillin, co-trimoxazole, chloramphenicol and ceftriaxone. Conclusion The proportion of drug resistant isolates has increased since the 1970s. All drugs currently used for the treatment of Salmonellosis but ciprofloxacin are not reliable for an empirical therapy. Alternative drugs should be included in the essential drug list and measures should be taken to re-enforce the drug use policy.
    BMC pharmacology & toxicology 09/2014; 15(1):51. DOI:10.1186/2050-6511-15-51
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    • "Additional examples are the emergence of resistant strains of serovars Virchow (Weill et al., 2004) and Heidelberg (Dutil et al., 2010). Similarly, many iNTS strains are resistant against ampicillin, chloramphenicol, kanamycin, streptomycin, trimethoprim, and cotrimoxazole (Gordon, 2008; Kingsley et al., 2009; Msefula et al., 2012). Therefore, there is a high need to (i) prevent further resistance development through the prudent use of antibiotics, (ii) improve measures that prevent spread of MDR strains, and (iii) discover new therapies for salmonelloses. "
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    ABSTRACT: Human infections by the bacterial pathogen Salmonella enterica represent major disease burdens worldwide. This highly ubiquitous species consists of more than 2600 different serovars that can be divided into typhoidal and non-typhoidal Salmonella (NTS) serovars. Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans. Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations. Recent advances in modeling both enteric fever and intestinal gastroenteritis in mice will facilitate investigation into both the bacterial- and host-mediated mechanisms involved in salmonelloses. Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity. This review outlines the differences in epidemiology, clinical manifestations, and the human immune response to typhoidal and NTS infections and summarizes the current thinking on why these differences might exist.
    Frontiers in Microbiology 08/2014; 5:391. DOI:10.3389/fmicb.2014.00391 · 3.99 Impact Factor
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