NorA Multidrug resistance Efflux pumps in Staphylococcus aureus

Gram positive organisms can be resistant to first line of antimicrobial agents and leading to complications in therapy. One of major reasons for these complications is efflux pumps. Apart from Drug resistance efflux pumps are used by bacteria to acquire nutrients, establish proper membrane charge and pH gradient, and to excrete out the by-products. [1] The efflux pumps are natural process that allows bacterial survival against multiple environmental challenges. There are lots of potential researches about gram positive efflux pumps and amongst those norA is much notable pump to be discussed here.

Types of efflux pumps

Efflux pumps in Gram positive bacteria are encoded by both plasmid and/or chromosomally expressed genes. For transmissible drug-specific efflux pumps are encoded by plasmids, whereas those which are multidrug resistance (MDR) are usually encoded by chromosome and not donated to other organisms. The plasmid based efflux pumps are multi copy in nature without any additional need of subsequent mutations. On the other hand, MDR occurs due to increased gene expression or occurrence of regulatory mutations.

Types of Efflux pumps in S aureus

Image: Multidrug efflux pumps in S. aureus which is categorized into four families of proteins: major facilitator super-family (MFS), the ATP-binding cassette (ABC) superfamily, the multidrug and toxin extrusion (MATE) family,and the small multidrug resistance (SMR) family.

NorA efflux pump

NorA was first identified efflux pump which is encoded by Staphylococcus aureus. As it is encoded by chromosome and can be well categorized under Multidrug resistance Efflux pumps. The function was identified when norA gene was cloned from the chromosome and based on its nucleotide sequence it was identified to encode major facilitator superfamily protein with 12 transmembrane segments.  NorA efflux pump is amongst the 8efflux pumps known. The others are NorB, NorC, MdeA, LmrS, SdrM, QacA and QacB efflux pumps. Check Figure for the classes of MDR efflux pumps in S. aureus.

Although the function was unknown until Yu et al in 2002 inhibited the protein motif force (pmf) that was necessary for norA gene to function. [3] Most of the active research was in the study of regulation. Most active regulators known are MgrA, NorR and NorG. MgrA fine tune the expression of norA gene and also norB gene and relates with the phophorylation status of the gene. NorG, a GntR-like regulatory protein found to bind the promoter of norA gene. Interestingly, disruption of norG does not affect the transcript of norA rather it provides susceptibility of S. aureus toward beta-lactam antibiotics. Thus norG has additional functions too apart from regulation of norA.

norA is highly expressed in MRSA isolates along with norB genes. Several researches have been experimented on detail role of this efflux pump and notably the promoter regulation of this gene. This is just an overview of one of the efflux pumps but there are more to this and research disclosed several pattern to disrupt the mechanism. Unfortunately there are way other mechanisms S. aureus bring forward for resistance.

Find the following video of a brief about of efflux pump

Additional Reading:

  1. Jang S. 2016. Multidrug efflux pumps in Staphylococcus aureus and their clinical implications. Journal of Microibology 54(1): 1-8
  2. Schindler, B.D; Kaatz, G.W 2016 Multidrug efflux pumps of Gram-positive bacteria. Drug Resistance Updates 27: 1-13

About Saumyadip

Science Communicator and Biologist. Keep interests in host-pathogen interaction research. Specifically bacterial infection mechanism, host infection evasion and immune susceptibility of host. PhD student at Academia Sinica Molecular and Cell Biology, Taiwan
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