Although Acinetobacter baumannii is well accepted as a nosocomial pathogen, only a few of the outer membrane proteins (OMPs) have been functionally characterized. In this study, we demonstrate the biological functions of AbuO, a homolog of TolC from Escherichia coli. Inactivation of abuO led to increased sensitivity to high osmolarity and oxidative stress challenge. The ⌬abuO mutant displayed increased susceptibility to antibiotics, such as amikacin, carbenicillin, ceftriaxone, meropenem, streptomycin, and tigecycline, and hospital-based disinfectants, such as benzalkonium chloride and chlorhexidine
Outer membrane proteins (OMPs) are known to have a pivotal role in bacterial physiology, such as adherence, invasion, and serum resistance, maintenance of cell structure, and binding a variety of substances, including passive and active transport (1). The archetypical OMP, TolC, has been considered to be a multifunctional protein due to its involvement in cell membrane integrity, acid tolerance, expulsion of metabolites, export of siderophores that are required in iron acquisition, export of plasmid and chromosomally encoded toxins, such as hemolysin, colicin V, and microcins, and virulence, as evident from studies in Enterobacter, Borrelia, Salmonella, Vibrio, Legionella, Francisella,. In E. coli, TolC is promiscuous because it supports the functioning of multidrug resistance efflux pumps, such as AcrD, AcrEF, and MdtABC (the resistance nodulation cell division [RND] superfamily) (11-13), EmrAB and EmrKY (the major facilitator superfamily [MFS]), and MacAB (the ATP-binding cassette [ABC] superfamily) (14-17). Although the functions of TolC homologs in many Gram-negative bacteria, such as E. coli, Vibrio vulnificus, Stenotrophomonas maltophilia, Enterobacter cloacae, and Yersinia pestis (5, 18-21), have been elucidated, the biological functions of TolC in an important human pathogen, Acinetobacter baumannii, have remained enigmatic so far.Multidrug-resistant (MDR) Acinetobacter strains kill up to 50% of infected patients, despite treatment with last resort drugs, and the resistance rates of such strains continue to escalate globally (22, 23). Significant increases in the number of A. baumannii strains that are resistant to carbapenems, cephalosporins, aminoglycosides, and fluoroquinolones with a diverse antibiotic resistome have been reported from hospitals in the United States and other countries (24-27). In our previous study, we demonstrated the role of antibiotic resistance genes and efflux pumps in mediating antimicrobial resistance in A. baumannii isolates from Ohio (28, 29). To date, few OMPs have been implicated in carbapenem resistance when their expression is reduced: CarO, Omp33 to -36, and an OprD homolog (30-32).In a continuation of our efforts toward understanding the origin/network of multidrug resistance in Acinetobacter, in this study, using genetic and molecular approaches, we demonstrate the role of a putative OMP (a homolog of TolC, designated AbuO) in bacterial stress physiology in general and a...