Basis for Success of Multidrug-Resistant Enterobacteriaceae

医院肺炎克雷伯菌感染的高发病率与抗生素耐药性，特别是碳青霉烯类耐药性相结合。在美国，碳青霉烯耐药主要是由肺炎克雷伯菌碳青霉烯酶（KPC）引起的。产生KPC的菌株对几乎所有β -内酰胺类抗生素都具有耐药性，由这些机会致病菌引起的感染很难治疗。这些多重耐药肺炎克雷伯菌菌株通常被称为经典肺炎克雷伯菌（cKp）。多位点序列258型（ST258）肺炎克雷伯菌是美国医院和世界其他地区最突出的含kpc的微生物。除了碳青霉烯类耐药性外，ST258和其他主要cKp菌株出现和成功的分子基础仍不完全确定。

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.