Multidrug Efflux Systems in Helicobacter cinaedi

Abstract

Helicobacter cinaedi causes infections, such as bacteremia, diarrhea and cellulitis in mainly immunocompromised patients. This pathogen is often problematic to analyze, and insufficient information is available, because it grows slowly and poorly in subculture under a microaerobic atmosphere. The first-choice therapy to eradicate H. cinaedi is antimicrobial chemotherapy; however, its use is linked to the development of resistance. Although we need to understand the antimicrobial resistance mechanisms of H. cinaedi, unfortunately, sufficient genetic tools for H. cinaedi have not yet been developed. In July 2012, the complete sequence of H. cinaedi strain PAGU 611, isolated from a case of human bacteremia, was announced. This strain possesses multidrug efflux systems, intrinsic antimicrobial resistance mechanisms and typical mutations in gyrA and the 23S rRNA gene, which are involved in acquired resistance to fluoroquinolones and macrolides, respectively. Here, we compare the organization and properties of the efflux systems of H. cinaedi with the multidrug efflux systems identified in other bacteria.

Keywords: Helicobacter cinaedi; antimicrobial resistance; efflux.

Figure 1

Drug efflux genes encoded in the genome of H. cinaedi PAGU 611. Chromosomal positions of drug efflux genes coding for putative inner membrane efflux transporters (red), outer membrane proteins (green), membrane fusion proteins (orange), and cytoplasmic proteins (light blue) are indicated by the kb (kilobase pair) in the H. cinaedi PAGU 611 genome [22]. Arrows correspond to the lengths and directions of the genes.

Figure 2

Phylogenetic trees for RND pumps of various bacteria. According to the COBALT program, the trees were constructed using the Fast evolution method and rendered with (A) Rectangle and (B) Radical. The accession numbers are shown in parentheses. The branches belonging to HCN_0595 and HCN_1563 of H. cinaedi PAGU 611 are shown in red and named “a” and “b”, respectively. The proteins are abbreviated (e.g., “AcrB_ECOL” stands for “AcrB of E. coli”). Abbreviations; PAER, Pseudomonas aeruginosa; CJEJ, Campylobacter jejuni; HPYR, Helicobacter pyroli; HCIN, Helicobacter cinaedi; ECOL, Escherichia coli; BSUI, Brucella suis; PPUT, Pseudomonas putida; AHYD, Aeromonas hydrophila.

Figure 3

Phylogenetic trees for the MATE pumps of various bacteria. According to the COBALT program, the trees were constructed using the Fast evolution method and rendered with (A) Rectangle and (B) Radical. The proteins are abbreviated (e.g., “NorM_ECOR” stands for “NorM of E. coli”). The accession numbers are shown in parentheses. HCN_0708 and HCN_0807 of H cinaedi PAGU 611 are shown in red. Abbreviations; HCIN, Helicobacter cinaedi; BTHE, Bacteroides thetaiotaomicron ; VCHO, Vibrio cholera; ECOL, Escherichia coli; VPAR, Vibrio parahaemolyticus; PAER, Pseudomonas aeruginosa; ABAU, Acinetobacter baumannii; NGOR, Neisseria gonorrhoeae; SAUR, Staphylococcus aureus; HPYR, Helicobacter pyroli.