The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinum

References

• Shin HJ, Kwon YS. Treatment of drug susceptible pulmonary tuberculosis. Tuberc Respir Dis. 2015;78(3):161–167.
   PubMed Web of Science ®Google Scholar
• Harms A, Maisonneuve E, Gerdes K. Mechanisms of bacterial persistence during stress and antibiotic exposure. Science. 2016;354(6318):aaf4268.
   PubMed Web of Science ®Google Scholar
• Zhang Y. Persisters, persistent infections and the Yin-Yang model. Emerg Microbes Infect. 2014;3(1):e3.
   PubMed Web of Science ®Google Scholar
• Levin-Reisman I, Ronin I, Gefen O, et al. Antibiotic tolerance facilitates the evolution of resistance. Science. 2017;355(6327):826–830.
   PubMed Web of Science ®Google Scholar
• Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nat Med. 2004;10(12):S122–S129.
   PubMed Web of Science ®Google Scholar
• Depardieu F, Podglajen I, Leclercq R, et al. Modes and modulations of antibiotic resistance gene expression. Clin Microbiol Rev. 2007;20(1):79–114.
   PubMed Web of Science ®Google Scholar
• Blair JM, Webber MA, Baylay AJ, et al. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015;13(1):42–51.
   PubMed Web of Science ®Google Scholar
• Amaral L, Martins M, Viveiros M. Enhanced killing of intracellular multidrug-resistant Mycobacterium tuberculosis by compounds that affect the activity of efflux pumps. J Antimicrob Chemother. 2007;59(6):1237–1246.
   PubMed Web of Science ®Google Scholar
• Bigger JW. Treatment of staphylococcal infections with penicillin – by intermittent sterilisation. Lancet. 1944;244:497–500.
   Google Scholar
• Keren I, Kaldalu N, Spoering A, et al. Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett. 2004;230(1):13–18.
   PubMed Web of Science ®Google Scholar
• Maisonneuve E, Shakespeare LJ, Jorgensen MG, et al. Bacterial persistence by RNA endonucleases. Proc Natl Acad Sci USA. 2011;108(32):13206–13211.
   PubMed Web of Science ®Google Scholar
• Keren I, Shah D, Spoering A, et al. Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli. J Bacteriol. 2004;186(24):8172–8180.
   PubMed Web of Science ®Google Scholar
• Durfee T, Hansen AM, Zhi H, et al. Transcription profiling of the stringent response in Escherichia coli. J Bacteriol. 2008;190(3):1084–1096.
   PubMed Web of Science ®Google Scholar
• Unoson C, Wagner EGH. A small SOS-induced toxin is targeted against the inner membrane in Escherichia coli. Mol Microbiol. 2008;70(1):258–270.
   PubMed Web of Science ®Google Scholar
• Gurnev PA, Ortenberg R, Dorr T, et al. Persister-promoting bacterial toxin TisB produces anion-selective pores in planar lipid bilayers. Febs Lett. 2012;586(16):2529–2534.
   PubMed Web of Science ®Google Scholar
• Dorr T, Vulic M, Lewis K. Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLoS Biol. 2010;8(2):e1000317.
   PubMed Web of Science ®Google Scholar
• Spoering AL, Vulic M, Lewis K. Glpd and PlsB participate in persister cell formation in Escherichia coli. J Bacteriol. 2006;188(14):5136–5144.
   PubMed Web of Science ®Google Scholar
• Hansen S, Lewis K, Vulic M. Role of global regulators and nucleotide metabolism in antibiotic tolerance in Escherichia coli. Antimicrob Agents Chemother. 2008;52(8):2718–2726.
   PubMed Web of Science ®Google Scholar
• Girgis HS, Harris K, Tavazoie S. Large mutational target size for rapid emergence of bacterial persistence. Proc Natl Acad Sci USA. 2012;109(31):12740–12745.
   PubMed Web of Science ®Google Scholar
• Pu Y, Zhao Z, Li Y, et al. Enhanced efflux activity facilitates drug tolerance in dormant bacterial cells. Mol Cell. 2016;62(2):284–294.
   PubMed Web of Science ®Google Scholar
• Fan XY, Tang BK, Xu YY, et al. Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria. Proc Natl Acad Sci USA. 2018;115(9):2210–2215.
   PubMed Web of Science ®Google Scholar
• McKinney JD, Honer Zu Bentrup K, Munoz-Elias EJ, et al. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature. 2000;406(6797):735–738.
   PubMed Web of Science ®Google Scholar
• Deb C, Lee CM, Dubey VS, et al. A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen. PLoS One. 2009;4(6):e6077.
   PubMed Web of Science ®Google Scholar
• Shi W, Zhang Y. Phoy2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. J Antimicrob Chemother. 2010;65(6):1237–1242.
   PubMed Web of Science ®Google Scholar
• Wang C, Mao Y, Yu J, et al. Phoy2 of mycobacteria is required for metabolic homeostasis and stress response. J Bacteriol. 2013;195(2):243–252.
   PubMed Web of Science ®Google Scholar
• Namugenyi SB, Aagesen AM, Elliott SR, et al. Mycobacterium tuberculosis PhoY proteins Promote persister formation by Mediating Pst/SenX3-RegX3 phosphate Sensing. MBio. 2017;8(4):e00494-17.
   PubMed Web of Science ®Google Scholar
• Epstein W. Progress in nucleic acid research and molecular biology. Prog Nucleic Acid Res Mol Biol. 2003;75:293–320.
   PubMed Web of Science ®Google Scholar
• Castaneda-Garcia A, Do TT, Blazquez J. The K+ uptake regulator TrkA controls membrane potential, pH homeostasis and multidrug susceptibility in Mycobacterium smegmatis. J Antimicrob Chemother. 2011;66(7):1489–1498.
   PubMed Web of Science ®Google Scholar
• Cholo MC, Boshoff HI, Steel HC, et al. Effects of clofazimine on potassium uptake by a Trk-deletion mutant of Mycobacterium tuberculosis. J Antimicrob Chemoth. 2006;57(1):79–84.
   PubMed Web of Science ®Google Scholar
• Moreira W, Aziz DB, Dick T. Boromycin kills mycobacterial persisters without detectable resistance. Front Microbiol. 2016;7:199.
   PubMed Web of Science ®Google Scholar
• Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, et al. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science. 1994;263(5147):678–681.
   PubMed Web of Science ®Google Scholar
• Rao SPS, Alonso S, Rand L, et al. The protonmotive force is required for maintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosis. P Natl Acad Sci USA. 2008;105(33):11945–11950.
   PubMed Web of Science ®Google Scholar
• Ali MK, Li X, Tang Q, et al. Regulation of inducible Potassium transporter KdpFABC by the KdpD/KdpE two-component system in Mycobacterium smegmatis. Front Microbiol. 2017;8:570.
   PubMed Web of Science ®Google Scholar
• Adams KN, Takaki K, Connolly LE, et al. Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell. 2011;145(1):39–53.
   PubMed Web of Science ®Google Scholar
• Liu Y, Zhou S, Deng Q, et al. Identification of a novel inhibitor of isocitrate lyase as a potent antitubercular agent against both active and non-replicating Mycobacterium tuberculosis. Tuberculosis. 2016;97:38–46.
   PubMed Web of Science ®Google Scholar
• Dharra R, Radhakrishnan VS, Prasad T, et al. Evaluation of in silico designed inhibitors targeting MelF (Rv1936) against Mycobacterium marinum within macrophages. Sci Rep. 2019;9(1):1–11.
   PubMed Web of Science ®Google Scholar
• Conlon BP, Rowe SE, Gandt AB, et al. Persister formation in Staphylococcus aureus is associated with ATP depletion. Nat Microbiol. 2016;1(5):16051.
   Web of Science ®Google Scholar
• Sassetti CM, Boyd DH, Rubin EJ. Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol. 2003;48(1):77–84.
   PubMed Web of Science ®Google Scholar
• Humphreys IR, Stewart GR, Turner DJ, et al. A role for dendritic cells in the dissemination of mycobacterial infection. Microbes Infect. 2006;8(5):1339–1346.
   PubMed Web of Science ®Google Scholar
• Levin-Reisman I, Gefen O, Balaban NQ. Tolerance and persistence promote the evolution of antibiotic resistance. Eur Biophys J Biophy. 2017;46:S73–S73.
   Web of Science ®Google Scholar
• Ballal A, Basu B, Apte SK. The Kdp-ATPase system and its regulation. J Biosciences. 2007;32(3):559–568.
   PubMed Web of Science ®Google Scholar
• Heermann R, Jung K. The complexity of the ‘simple’ two-component system KdpD/KdpE in Escherichia coli. FEMS Microbiol Lett. 2010;304(2):97–106.
   PubMed Web of Science ®Google Scholar
• Heermann R, Altendorf K, Jung K. The N-terminal input domain of the sensor kinase KdpD of Escherichia coli stabilizes the interaction between the cognate response regulator KdpE and the corresponding DNA-binding site. J Biol Chem. 2003;278(51):51277–51284.
   PubMed Web of Science ®Google Scholar
• Bretl DJ, Demetriadou C, Zahrt TC. Adaptation to environmental stimuli within the host: two-component signal transduction systems of Mycobacterium tuberculosis. Microbiol Mol Biol R. 2011;75(4):566–582.
   PubMed Web of Science ®Google Scholar
• Huang CS, Pedersen BP, Stokes DL. Crystal structure of the potassium-importing KdpFABC membrane complex. Nature. 2017;546(7660):681–685.
   PubMed Web of Science ®Google Scholar
• Mc DW. Microbial persistence. Yale J Biol Med. 1958;30(4):257–291.
   PubMedGoogle Scholar
• Brauner A, Fridman O, Gefen O, et al. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat Rev Microbiol. 2016;14(5):320–330.
   PubMed Web of Science ®Google Scholar
• Walderhaug MO, Polarek JW, Voelkner P, et al. Kdpd and KdpE, proteins that control expression of the kdpABC operon, are members of the two-component sensor-effector class of regulators. J Bacteriol. 1992;174(7):2152–2159.
   PubMed Web of Science ®Google Scholar
• Xue T, You Y, Hong D, et al. The Staphylococcus aureus KdpDE two-component system couples extracellular K+ sensing and Agr signaling to infection programming. Infect Immun. 2011;79(6):2154–2167.
   PubMed Web of Science ®Google Scholar
• Rao M, Streur TL, Aldwell FE, et al. Intracellular pH regulation by Mycobacterium smegmatis and Mycobacterium bovis BCG. Microbiology. 2001;147(Pt 4):1017–1024.
   PubMed Web of Science ®Google Scholar
• Bakker EP, Mangerich WE. Interconversion of components of the bacterial proton motive force by electrogenic potassium transport. J Bacteriol. 1981;147(3):820–826.
   PubMed Web of Science ®Google Scholar
• Sielaff H, Duncan TM, Borsch M. The regulatory subunit epsilon in Escherichia coli FOF1-ATP synthase. Biochim Biophys Acta Bioenerg. 2018;1859(9):775–788.
   PubMed Web of Science ®Google Scholar
• Fillingame RH. Coupling H+ transport and ATP synthesis in F1F0-ATP synthases: glimpses of interacting parts in a dynamic molecular machine. J Exp Biol. 1997;200(Pt 2):217–224.
   PubMed Web of Science ®Google Scholar
• Parry BR, Surovtsev IV, Cabeen MT, et al. The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity. Cell. 2014;156(1–2):183–194.
   PubMed Web of Science ®Google Scholar
• Pu Y, Li Y, Jin X, et al. ATP-dependent dynamic protein aggregation regulates bacterial dormancy depth critical for antibiotic tolerance. Mol Cell. 2019;73(1):143–156e4.
   PubMed Web of Science ®Google Scholar
• Patel A, Malinovska L, Saha S, et al. ATP as a biological hydrotrope. Science. 2017;356(6339):753–756.
   PubMed Web of Science ®Google Scholar
• Wang X, Lord DM, Cheng HY, et al. A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nat Chem Biol. 2012;8(10):855–861.
   PubMed Web of Science ®Google Scholar
• Verstraeten N, Knapen WJ, Kint CI, et al. Obg and membrane depolarization are part of a microbial bet-hedging strategy that leads to antibiotic tolerance. Mol Cell. 2015;59(1):9–21.
   PubMed Web of Science ®Google Scholar
• Cheng HY, Soo VW, Islam S, et al. Toxin GhoT of the GhoT/GhoS toxin/antitoxin system damages the cell membrane to reduce adenosine triphosphate and to reduce growth under stress. Environ Microbiol. 2014;16(6):1741–1754.
   PubMed Web of Science ®Google Scholar
• Girgis HS, Hottes AK, Tavazoie S. Genetic architecture of intrinsic antibiotic susceptibility. PLoS One. 2009;4(5):e5629.
   PubMed Web of Science ®Google Scholar
• Paulsen IT, Brown MH, Skurray RA. Proton-dependent multidrug efflux systems. Microbiol Rev. 1996;60(4):575–608.
   PubMedGoogle Scholar
• Molina-Quiroz RC, Silva-Valenzuela C, Brewster J, et al. Cyclic AMP regulates bacterial persistence through repression of the oxidative stress response and SOS-dependent DNA repair in uropathogenic Escherichia coli. MBio. 2018;9(1):e02144–17.
   PubMed Web of Science ®Google Scholar
• Shan Y, Brown Gandt A, Rowe SE, et al. ATP-dependent persister formation in Escherichia coli. MBio. 2017;8(1):e02267–16.
   PubMed Web of Science ®Google Scholar