RND family efflux transporters

Among the several classes of bacterial Multidrug Resistance efflux pumps (see more detail in the page on ABC type multidrug transport systems) is the resistance/nodulation/division (RND) superfamily.  The activity of an efflux pump depends on the type of energy source a system uses; RND pumps use the proton- motive force. 

The RND family includes several members that are relevant to antibiotic resistance in Gram-negative bacteria.  Crystallographic analysis of AcrB, a model member of the RND family, revealed that this protein forms a homotrimer, that associates into a tripartite complex comprising an outer membrane protein (OMP, TolC) and two copies of a periplasmic membrane-fusion protein (MFP, AcrA;  (Murakami et al., 2002; Nakashima et al., 2011).

RND efflux pumps perform several different functional roles in addition to mediating antibiotic resistance.  Some of the most relevant roles so far identified include involvement in bacterial virulence.

 

RND EFFLUX PUMP GENES IN ORIENTIA 

tolC – outer membrane protein

In O. tsutsugamushi, examination of the genomes of 14 isolates, plus the genome of O. chuto, revealed that only one component of the RND efflux pump system appears to be be readily identifiable.  This component is that part homologus with tolC outer membrane proteins.  This component was present in the genomes of all of the isolates examined.  As with other antibiotic resistance genes in Orientia, tolC showed substantial variation at both the nucleic acid and amino acid levels.  No obvious mutational differences between isolates can be identified which might be thought to be associated with antibiotic resistance.  

The tolC gene is found at positions 379572..380948 in the Boryong isolate genome.

 

AcrA or similar periplasmic membrane-fusion protein

The periplasmic membrane-fusion protein compone tof the RND efflux system appear to be absent in Orientia.  This component is present in some members of the genus Rickettsia, including R. bellii, R. felis, R. akari, and probably in all members of the spotted fever group (such as R. rickettsii and R. conorii). 

The gene is absent in a few members of Rickettsia, specifically R. candensis, or in the typhus group species R. prowazekii and R. typhi.

The gene also appears to be absent in other groups of the rickettsiales, including Neorickettsia, Ehrlichia, Anaplasma and Wolbachia.