Basis for Success of Multidrug-Resistant Enterobacteriaceae

医院中肺炎克雷伯菌感染的高发病率与抗生素耐药性，特别是碳青霉烯耐药性有关。在美国，碳青霉烯类耐药主要是由K。肺炎碳青霉烯酶（KPC）。产生KPC的菌株对几乎所有的β-内酰胺类抗生素都有抗性，并且由这些机会致病菌引起的感染难以治疗。肺炎克雷伯氏菌菌株通常被称为经典克雷伯氏菌。pneumoniae（cKp）。多位点序列型258（ST 258）K.肺炎克雷伯氏菌是美国医院和全球其他地区最主要的含KPC的生物体。除了碳青霉烯耐药之外，ST 258和其他突出的cKp菌株的出现和成功的分子基础仍然不完全确定。 虽然大多数K。肺炎克雷伯氏菌感染发生在医院，一组单独的菌株被称为高毒力克雷伯氏菌。肺炎克雷伯氏菌（hvKp）在健康个体中引起社区获得性感染。hvKp的分子遗传学主要由基于多位点序列分型的三个克隆群（CG）主导，即CG 23、CG 65和CG 86。hvKp表型主要归因于在历史上不存在于cKp中的质粒上编码的特异性毒力分子。然而，最近出现了多药耐药和高毒力表型（MDR kvKp）相结合的菌株。这些菌株在社区和医疗环境中的出现强调了开发用于预防和/或治疗由这些生物体引起的感染的替代方法的需要。 我们假设cKp或新出现的MDR hvKp的成功部分是由于这些微生物规避先天免疫系统破坏的能力（例如，被宿主嗜中性粒细胞和血清补体杀死）。 cKp感染主要发生在具有显著共病和/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受试者中。 如果我们的假设是正确的，支持宿主对这些生物体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.