Basis for Success of Multidrug-Resistant Enterobacteriaceae

肺炎克雷伯菌医院感染的高发病率与抗生素耐药性，特别是碳青霉烯类耐药性有关。在美国，碳青霉烯类耐药主要由肺炎克雷伯菌碳青霉烯酶(KPC)引起。产生KPC的菌株对几乎所有的β-内酰胺类抗生素都具有耐药性，由这些机会性病原体引起的感染很难治疗。这些多药耐药(MDR)肺炎克雷伯菌常被称为经典肺炎克雷伯菌(CKP)。多位点序列类型258(ST258)肺炎克雷伯菌是美国医院和世界其他地区最常见的含有KPC的微生物。除了对碳青霉烯类抗生素的耐药性外，ST258和其他主要CKP菌株的出现和成功的分子基础仍未完全确定。 虽然大多数肺炎克雷伯菌感染发生在医院，但另一组被称为超强毒力肺炎克雷伯菌(HvKp)的菌株会在其他健康的个人中引起社区获得性感染。根据多位点序列分型，hvKp的分子系统发育主要由三个克隆群(CG)主导，即CG23、CG65和CG86。HvKp的表型很大程度上归因于编码在质粒上的特定毒力分子，而这些分子在历史上并不存在于CKP中。然而，最近出现了多药耐药和超强毒力表型(MdrkvKp)相结合的菌株。这种菌株在社区和保健环境中的出现突出表明，需要开发替代办法来预防和/或治疗由这些微生物引起的感染。 我们假设CKP或新兴的MDR hvKp的成功部分是由于这些微生物能够避开天然免疫系统的破坏(例如，宿主中性粒细胞和血清补体的杀伤)。感染CKP主要发生在有显著共病和/或免疫抑制的个体中，而由hvKp引起的感染通常发生在其他健康的人中。如果我们的假设是正确的，加强宿主对这两种微生物的反应可能是一种有效的免疫预防和/或免疫治疗方法。

The high incidence of Klebsiella pneumoniae infections in hospitals is compounded by antibiotic resistance, and notably carbapenem resistance. In the United States, carbapenem-resistance is conferred largely by K. pneumoniae carbapenemase (KPC). Strains that produce KPC are resistant to virtually all beta-lactam antibiotics and infections caused by these opportunistic pathogens are difficult to treat. These multidrug resistant (MDR) K. pneumoniae strains are often referred to as classical K. pneumoniae (cKp). Multilocus sequence type 258 (ST258) K. pneumoniae are the most prominent KPC-containing organisms in U.S. hospitals and other regions worldwide. Outside of carbapenem resistance, the molecular underpinnings of the emergence and success of ST258 and other prominent cKp strains remain incompletely determined. Although the majority of K. pneumoniae infections occur in hospitals, a separate group of strains known as hypervirulent K. pneumoniae (hvKp) cause community-acquired infections in otherwise healthy individuals. The molecular phylogeny of hvKp is predominated by three clonal groups (CGs) based on multilocus sequence typing, namely CG23, CG65, and CG86. The hvKp phenotype is attributed largely to specific virulence molecules encoded on plasmids that were historically not present in cKp. However, there has been recent emergence of strains with the combination of multidrug resistance and hypervirulence phenotypes (MDR kvKp). The emergence of such strains in both community and healthcare settings underscores the need for development of alternative approaches for prevention and/or treatment of infections caused by these organisms. We hypothesize that the success of cKp or emerging MDR hvKp is in part due to the ability of these microbes to circumvent destruction by the innate immune system (e.g., killing by host neutrophils and serum complement). Infections with cKp primarily occur in individuals with significant co-morbidities and/or immunosuppression, whereas those caused by hvKp often occur in otherwise healthy subjects. If our hypothesis is correct, bolstering the host response to either of these organisms could be an effective immunoprophylaxis and/or immunotherapy approach.