MomL inhibits bacterial antibiotic resistance through the starvation stringent response pathway

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.

Regulation of nitrogen starvation responses by the alarmone(p)ppGpp in rice

Nitrogen is an essential macronutrient for all living organisms and is critical for crop productivity and quality.In higher plants,inorganic nitrogen is absorbed through roots and then assimilated into amino acids by the highly conserved glutamine synthetase/glutamine:2-oxoglutarate aminotransferase(GS/GOGAT)cycle.How nitrogen metabolism and nitrogen starvation responses of plants are regulated remains largely unknown.Previous studies revealed that mutations in the rice ABNORMAL CYTOKININ RESPONSE1(ABC1)gene encoding Fd-GOGAT cause a typical nitrogen deficiency syndrome.Here,we show that ARE2(for ABC1 REPRESSOR2)is a key regulator of nitrogen starvation responses in rice.The are2 mutations partially rescue the nitrogen-deficient phenotype of abc1 and the are2 mutants show enhanced tolerance to nitrogen deficiency,suggesting that ARE2 genetically interacts with ABC1/Fd-GOGAT.ARE2 encodes a chloroplast-localized Rel A/Spo T homolog protein that catalyzes the hydrolysis of guanosine pentaphosphate or tetraphosphate(p)pp Gpp,an alarmone regulating the stringent response in bacteria under nutritional stress conditions.The are2 mutants accumulate excessive amounts of(p)pp Gpp,which correlate with lower levels of photosynthetic proteins and higher amino acid levels.Collectively,these observations suggest that the alarmone(p)pp Gpp mediates nitrogen stress responses and may constitute a highly conserved mechanism from bacteria to plants.