Antibiotic resistance in Pseudomonas aeruginosa is a serious concern in healthcare systems. Among the determinants of antibiotic resistance in P. aeruginosa , efflux pumps belonging to the resistance–nodulation–division (RND) family confer resistance to a broad range of antibacterial compounds. The MexXY efflux system is widely overexpressed in P. aeruginosa isolates from cystic fibrosis (CF) patients. MexXY can form functional complexes with two different outer membrane factors (OMFs), OprA and OprM. In this study, using state-of-the-art genetic tools, the substrate specificities of MexXY–OprA and MexXY–OprM complexes were determined. Our results show, for the first time, that the substrate profile of the MexXY system from P. aeruginosa PA7 can vary depending on which OM factor (OprM or OprA) it complexes with. While both MexXY–OprA and MexXY–OprM complexes are capable of effluxing aminoglycosides, the bi-anionic β-lactam molecules carbenicillin and sulbenicillin were found to only be the substrate of MexXY–OprA. Our study therefore shows that by partnering with different OMF proteins MexY can expand its substrate profile.
Bacteria have evolved multiple protein secretion systems to survive and cope with surrounding environmental stresses. So far, there are seven secretion systems (type I to type VII), which have been identified and demonstrated the structural and molecular mechanisms. Among them, type three secretion system (T3SS), hallmark of acute infection, is considered as the most complicated system and can translocate effector proteins directly into host cell through a needle-like apparatus. Type six secretion system (T6SS) targets both prokaryotic and eukaryotic cells using a bacteriophage-like structure and plays a role in pathogenesis and bacterial competition. This review is based on our understanding of comparison of the structure, regulation, function and application between T3SS and T6SS. Understanding the structural and functional mechanisms, as well as the difference and relationship between these two secretion systems will help our understanding of bacterial pathogenesis and interspecies interaction.
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