Strain variation and anomalous climate synergistically influence cholera pandemics

Explanations for the genesis and propagation of recurrent cholera pandemics since 1817 have remained elusive. Evolutionary change of the pathogen is presumed to have been a dominant factor behind the 7th El Tor pandemic, but little is known to support this hypothesis for preceding pandemics. We investigate the concomitant roles of climate and putative strain variation for the 6th cholera pandemic (1899-1923; the one with the highest ever associated mortality in India), using newly assembled historical records for climate variables and cholera deaths for Bengal, Assam, Bihar and Bombay provinces in former British India. We compare this historical pandemic with the 7th (El Tor) one and with the temporary emergence of the O139 strain in Bangladesh and globally. Finally, we ran multi-model climate simulations to infer past and future long-term means of rainfall distributions on the basis of 39 models for 1861-2100, and for different periods of 50 years (1875-1925; 1975-2025 and 2050-2100). The 6th cholera pandemic featured a large scale synchronisation with a delay of a few years in both seasonal and interannual cholera variability over the endemic Bengal region during the El Nino event of 1904-07. Additional evidence supporting the establishment of a new strain includes a shift of cholera incidence to older age groups, an increase in the case fatality rate and the suppression of the spring cholera peak. The 6th cholera pandemic of Indian origin was associated with a novel and particularly invasive strain of new territory, and also with some delay, of endemic parts of India that act as a genetic regional reservoir of the disease. Climate anomalies appear to have played an important role in facilitating the establishment of this invasive strain, with environmental conditions similar to those underlying strain changes associated with ENSO in today Bangladesh. The evolutionary change of pathogens can act synergistically with climatic conditions in the replacement and propagation of emerging strains, as was the case in cholera 7th pandemic. Increased climate variability and extremes under global warming would thus provide windows of opportunity for emerging new pathogens.

Potency of gastrointestinal colonization and virulence of Candida auris in a murine endogenous candidiasis

Background Candida auris infections have recently emerged worldwide, and this species is highly capable of colonization and is associated with high levels of mortality. However, strain-dependent differences in colonization capabilities and virulence have not yet been reported. Objectives In the present study, we aimed to clarify the differences between clinically isolated invasive and non-invasive strains of C. auris. Methods We evaluated colonization, dissemination, and survival rates in wild C57BL/6J mice inoculated with invasive or non-invasive strains of C. auris under cortisone acetate immunosuppression, comparing with those of Candida albicans and Candida glabrata infections. We also evaluated the potency of biofilm formation. Results Stool fungal burdens were significantly higher in mice inoculated with the invasive strains than in those infected with the non-invasive strain. Along with intestinal colonization, liver and kidney fungal burdens were also significantly higher in mice inoculated with the invasive strains. In addition, histopathological findings revealed greater dissemination and colonization of the invasive strains. Regarding biofilm-forming capability, the invasive strain of C. auris exhibited a significantly higher capacity of producing biofilms. Moreover, inoculation with the invasive strains resulted in significantly greater loss of body weight than that noted following infection with the non-invasive strain. Conclusions Invasive strains showed higher colonization capability and rates of dissemination from gastrointestinal tracts under cortisone acetate immunosuppression than non-invasive strains, although the mortality rates caused by C. auris were lower than those caused by C. albicans.

Increased Pilus Production Conferred by a Naturally Occurring Mutation Alters Host-Pathogen Interaction in Favor of Carriage in Streptococcus pyogenes

ABSTRACT Studies of the human pathogen group A Streptococcus (GAS) define the carrier phenotype to be an increased ability to adhere to and persist on epithelial surfaces and a decreased ability to cause disease. We tested the hypothesis that a single amino acid change (Arg135Gly) in a highly conserved sensor kinase (LiaS) of a poorly defined GAS regulatory system contributes to a carrier phenotype through increased pilus production. When introduced into an emm serotype-matched invasive strain, the carrier allele (the gene encoding the LiaS protein with an arginine-to-glycine change at position 135 [liaS R135G]) recapitulated a carrier phenotype defined by an increased ability to adhere to mucosal surfaces and a decreased ability to cause disease. Gene transcript analyses revealed that the liaS mutation significantly altered transcription of the genes encoding pilus in the presence of bacitracin. Elimination of pilus production in the isogenic carrier mutant decreased its ability to colonize the mouse nasopharynx and to adhere to and be internalized by cultured human epithelial cells and restored the virulence phenotype in a mouse model of necrotizing fasciitis. We also observed significantly reduced survival of the isogenic carrier mutant compared to that of the parental invasive strain after exposure to human neutrophils. Elimination of pilus in the isogenic carrier mutant increased the level of survival after exposure to human neutrophils to that for the parental invasive strain. Together, our data demonstrate that the carrier mutation (liaS R135G) affects pilus expression. Our data suggest new mechanisms of pilus gene regulation in GAS and that the invasiveness associated with pilus gene regulation in GAS differs from the enhanced invasiveness associated with increased pilus production in other bacterial pathogens.

Genome Sequence ofPorphyromonas gingivalisStrain AJW4

Porphyromonas gingivalisis associated with oral and systemic diseases. Strain-specificP. gingivalisinvasion phenotypes have been correlated with disease presentation in infected laboratory animals. Here, we present the genome sequence of AJW4, a minimally invasive strain, with a single contig of 2,372,492 bp and a G+C content of 48.27%.

Natural Variant of Collagen-Like Protein A in Serotype M3 Group A Streptococcus Increases Adherence and Decreases Invasive Potential

Group AStreptococcus(GAS) predominantly exists as a colonizer of the human oropharynx that occasionally breaches epithelial barriers to cause invasive diseases. Despite the frequency of GAS carriage, few investigations into the contributory molecular mechanisms exist. To this end, we identified a naturally occurring polymorphism in the gene encoding the streptococcal collagen-like protein A (SclA) in GAS carrier strains. All previously sequenced invasive serotype M3 GAS possess a premature stop codon in thesclAgene truncating the protein. The carrier polymorphism is predicted to restore SclA function and was infrequently identified by targeted DNA sequencing in invasive strains of the same serotype. We demonstrate that a strain with the carriersclAallele expressed a full-length SclA protein, while the strain with the invasivesclAallele expressed a truncated variant. An isoallelic mutant invasive strain with the carriersclAallele exhibited decreased virulence in a mouse model of invasive disease and decreased multiplication in human blood. Further, the isoallelic invasive strain with the carriersclAallele persisted in the mouse nasopharynx and had increased adherence to cultured epithelial cells. Repair of the premature stop codon in the invasivesclAallele restored the ability to bind the extracellular matrix proteins laminin and cellular fibronectin. These data demonstrate that a mutation in GAS carrier strains increases adherence and decreases virulence and suggest selection against increased adherence in GAS invasive isolates.