报告题目：A Salmonella enterica Paratyphi A Stk fimbrial gene polymorphism: spontaneous neutral variation or an immune evasion-selected phenomenon
报 告 人：Dr. Kumar RAJAKUMAR
Clinical Senior Lecturer
Department of Infection, Immunity and Inflammation
University of Leicester, UK
Over the last two decades Salmonella enterica serovar Paratyphi A has matched or even on occasion surpassed Salmonella Typhi as the principal cause of enteric fever in many parts of the world. At present there are no licenced vaccines against this pathogen, and contrary to historical misconceptions S. Paratyphi A causes an illness which is indistinguishable based on symptoms, signs and severity from that of S. Typhi. Like its sister organism, S. Paratyphi A is a human-restricted pathogen which is increasingly prone to exhibiting multiple-antibiotic resistance. All S. enterica serovars studied to date are known to possess diverse repertoires of multiple, distinct fimbrial systems, several of which have been implicated in pathogenesis, biofilm formation and/or host-adaptation. The 7-gene stk operon codes for a γ4 fimbrial clade chaperone-usher fimbrial system and is found in ~30 % of Salmonella serovars, including S. Paratyphi A but not S. Typhi. Intriguingly, the S. Paratyphi A stkF gene which codes for a likely tip-located adhesin, is unique amongst all sequenced counterparts in exhibiting a polymorphism that is postulated to have arisen from slipped strand mispairing and/or recombination. Critically, this polymorphism appears to govern ON-OFF switching of the stkF gene and its cognate fimbrial system. This presentation is focussed on the basis, consequence, and potential underlying evolutionary and clinical implications of this hypothesised stkF switch. To conclude, alternative models for this phenomenon will be explored, including the novel idea that the bacterium itself may be acting as a 'public health practitioner' by notifying underlying aspects of health care provision in different regions of the globe.