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Pathoadaptive mutations that enhance virulence: genetic organization of the cadA regions of Shigella spp.

ABSTRACT: Pathoadaptive mutations improve the fitness of pathogenic species by modification of traits that interfere with factors (virulence and ancestral) required for survival in host tissues. A demonstrated pathoadaptive mutation is the loss of lysine decarboxylase (LDC) expression in Shigella species that have evolved from LDC-expressing Escherichia coli. Previous studies demonstrated that the product of LDC activity, cadaverine, blocks the action of Shigella enterotoxins and that the gene encoding LDC, cadA, was abolished by large chromosomal deletions in each Shigella species. To better understand the nature and evolution of these pathoadaptive mutations, remnants of the cad region were sequenced from the four Shigella species. These analyses reveal novel gene arrangements in this region of the pathogens' chromosomes. Insertion sequences, a phage genome, and/or loci from different positions on the ancestral E. coli chromosome displaced the cadA locus to form distinct genetic linkages that are unique to each Shigella species. Hybridization studies, using an E. coli K-12 microarray, indicated that the genes displaced to form the novel linkages still remain in the Shigella genomes. None of these novel gene arrangements were observed in representatives of all E. coli phylogenies. Collectively, these observations indicate that inactivation of the cadA antivirulence gene occurred independently in each Shigella species. The convergent evolution of these pathoadaptive mutations demonstrates that, following evolution from commensal E. coli, strong pressures in host tissues selected Shigella clones with increased fitness and virulence through the loss of an ancestral trait (LDC). These observations strongly support the role of pathoadaptive mutation as an important pathway in the evolution of pathogenic organisms.

SUBMITTER: Day WA

PROVIDER: S-EPMC98836 | biostudies-literature | 2001 Dec

REPOSITORIES: biostudies-literature

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Pathoadaptive mutations that enhance virulence: genetic organization of the cadA regions of Shigella spp.

Day W A WA Fernández R E RE Maurelli A T AT

Infection and immunity 20011201 12

Pathoadaptive mutations improve the fitness of pathogenic species by modification of traits that interfere with factors (virulence and ancestral) required for survival in host tissues. A demonstrated pathoadaptive mutation is the loss of lysine decarboxylase (LDC) expression in Shigella species that have evolved from LDC-expressing Escherichia coli. Previous studies demonstrated that the product of LDC activity, cadaverine, blocks the action of Shigella enterotoxins and that the gene encoding LD ...[more]

PMID: 11705922

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Project description:BackgroundShigella spp., facultative anaerobic bacilli of the family Enterobacteriaceae, are one of the most common causes of diarrheal diseases in human worldwide which have become a significant public health burden. So, we aimed to analyze the antimicrobial phenotypes and to elucidate the molecular mechanisms underlying resistance to cephalosporins and fluoroquinolones in Shigella isolates from patients with diarrhea in Shanxi Province.ResultsDuring 2006-2016, we isolated a total of 474 Shigella strains (including 337 S. flexneri and 137 S. sonnei). The isolates showed high rates of resistance to traditional antimicrobials, and 26, 18.1 and 3.0% of them exhibited resistance to cephalosporins, fluoroquinolones and co-resistance to cephalosporins and fluoroquinolones, respectively. Notably, 91.1% of these isolates, including 22 isolates that showed an ACTSuT profile, exhibited multidrug resistance (MDR). The resistance rates to cephalosporins in S. sonnei isolates were higher than those in S. flexneri. Conversely, the resistance rates to fluoroquinolones were considerably higher in S. flexneri isolates. Among the 123 cephalosporins-resistant isolates, the most common extended-spectrum beta-lactamase gene was blaTEM-1, followed by blaCTX-M, blaOXA-1, and blaSHV-12. Six subtypes of blaCTX-M were identified, blaCTX-M-14 (n = 36) and blaCTX-M-55 (n = 26) were found to be dominant. Of all the 86 isolates with resistance to fluoroquinolones and having at least one mutation (Ser83Leu, His211Tyr, or Asp87Gly) in the the quinolone resistance-determining regions of gyrA, 79 also had mutation of parC (Ser80Ile), whereas 7 contained plasmid-mediated quinolone resistance genes including qnrA, qnrB, qnrS, and aac(60)-Ib-cr. Furthermore, pulsed-field gel electrophoresis analysis (PFGE) showed a considerable genetic diversity in S. flexneri isolates. However, the S. sonnei isolates had a high genetic similarity.ConclusionsCoexistence of diverse resistance genes causing the emergence and transmission of MDR might render the treatment of shigellosis difficult. Therefore, continuous surveillance might be needed to understand the actual disease burden and provide guidance for shigellosis.

Dataset Information

Pathoadaptive mutations that enhance virulence: genetic organization of the cadA regions of Shigella spp.

Publications

Pathoadaptive mutations that enhance virulence: genetic organization of the cadA regions of Shigella spp.

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