Global Proteome Profiling Reveals Drug-Resistant Traits in Elizabethkingia meningoseptica: An Opportunistic Nosocomial Pathogen

Abstract

Elizabethkingia meningoseptica is Gram-negative, rod-shaped opportunistic bacterial pathogen increasingly reported in hospital-acquired outbreaks. This bacterium is well known to thrive in the hospital environment. One of the leading causes of meningitis in pediatric and immune-compromised patients, E. meningoseptica has been noted as a ''pathogen of interest'' in the context of nosocomial diseases associated with device-related infections in particular. This pathogen's multidrug-resistant phenotype and attendant lack of adequate molecular mechanistic data limit the current approaches for its effective management in hospitals and public health settings. This study provides the global proteome of E. meningoseptica. The reference strain E. meningoseptica ATCC 13253 was used for proteomic analysis using high-resolution Fourier transform mass spectrometry. The study provided translational evidence for 2506 proteins of E. meningoseptica. We identified multiple metallo-b-lactamases, transcriptional regulators, and efflux transporter proteins associated with multidrug resistance. A protein Car D, which is an enzyme of the carbapenem synthesis pathway, was also discovered in E. meningoseptica. Further, the proteomics data were harnessed for refining the genome annotation. We discovered 39 novel protein-coding genes and corrected four existing translations using proteogenomic workflow. Novel translations reported in this study enhance the molecular data on this organism, thus improving current databases. We believe that the in-depth proteomic data presented in this study offer a platform for accelerated research on this pathogen. The identification of multiple proteins, particularly those involved in drug resistance, offers new future opportunities to design novel and specific antibiotics against infections caused by E. meningoseptica.

<p>Molecular Characteristics and Antimicrobial Susceptibility Profiles of <em>Elizabethkingia</em> Clinical Isolates in Shanghai, China</p>

“…Multiple resistance genes and drug efflux systems in Elizabethkingia have been demonstrated by genomic and proteomic analysis. 35,36 In this study, the high carriage rate of bla CME , bla BlaB and bla GOB genes was consistent with the broad-spectrum resistance to β-lactams including carbapenems. Nevertheless, piperacillintazobactam and cefoperazone-sulbactam were active in vitro against Elizabethkingia, in accordance with the results of a previous study where both combinations showed reasonable in vitro activity (70-85% and 65-80% of susceptibility rate, respectively) against 170 clinical Elizabethkingia isolates in China.…”

Clinical manifestations, antimicrobial resistance and genomic feature analysis of the multi-drug resistance Elizabethkingia strains

“…Elizabethkingia isolates were frequently resistant to many antimicrobial agents, including most β-lactams and inhibitors, aminoglycosides, macrolides, tetracycline, vancomycin, and carbapenems (25). They exhibited variable susceptibility to piperacillin, piperacillin-tazobactam, uoroquinolones, minocycline, tigecycline, and trimethoprim-sulfamethoxazole(26).…”

Epidemiological Study and Analysis of Risk Factors for Elizabethkingia Meningoseptica Infection in a Large General Hospital in China

“…Epidemiological reports related to E. meningoseptica infection show that Taiwan had the highest number of reported cases, with a mortality rate of 63.2% [3]. Reports from South Korea, Spain, the United Kingdom, India, and Taiwan show that E. meningoseptica can survive in hospital sinks, faucets, humidi ers, and other ward environments and on medical equipment and can cause nosocomial outbreaks [20][21][22][23]. These ndings and the broad resistance of E. meningoseptica in our hospital indicate that E. meningoseptica infection is a serious threat to people's health and lives; furthermore, the possibility that serious nosocomial infections may recur in speci c populations, such as ICU patients or those with weakened immunity, cannot be ruled out.…”