MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway

Abstract

Antibiotic resistance in gram-negative pathogens has become one of the most serious global public health threats. The role of the N-acyl homoserine lactone (AHL)-mediated signaling pathway, which is widespread in gram-negative bacteria, in the bacterial resistance process should be studied in depth. Here, we report a degrading enzyme of AHLs, MomL, that inhibits the antibiotic resistance of Pseudomonas aeruginosa through a novel mechanism. The MomL-mediated reactivation of kanamycin is highly associated with the relA-mediated starvation stringent response. The degradation of AHLs by MomL results in the inability of LasR to activate relA, which, in turn, stops the activation of downstream rpoS. Further results show that rpoS directly regulates the type VI secretion system H2-T6SS. Under MomL treatment, inactivated RpoS fails to regulate H2-T6SS; therefore, the expression of effector phospholipase A is reduced, and the adaptability of bacteria to antibiotics is weakened. MomL in combination with kanamycin is effective against a wide range of gram-negative pathogenic bacteria. Therefore, this study reports a MomL-antibiotic treatment strategy on antibiotic-resistant bacteria and reveals its mechanism of action.

Dual functions: A coumarin–chalcone conjugate inhibits cyclic‐di‐GMP and quorum‐sensing signaling to reduce biofilm formation and virulence of pathogens

“…Previous studies have reported that the nutrient starvation response might enhance antibiotic resistance 37,38 . To evaluate whether C9 could be a promising alternative against P. aeruginosa infections under these conditions, survivability tests of P. aeruginosa under starvation and oxidative stress were performed.…”

“…The survival rate of PAO1 under starvation and oxidative stress was determined as previously described, with slight modifications 38 , 75 . The overnight bacterial culture was centrifuged, and the supernatant was discarded and then resuspended in the corresponding medium separately according to different severe conditions.…”

Phage‐displayed heptapeptide sequence conjugation significantly improves the specific targeting ability of antimicrobial peptides against Staphylococcus aureus

“…Bacterial resistance to antibiotics occurs naturally. However, extensive and irregular use of antibiotics has accelerated the evolution and mutation of drug‐resistant strains 1 , 2 , 3 , 4 , 5 . Therefore, it is important to identify and develop new antibacterial drugs that are safe and efficient.…”