Abstract:
:Evolutionary trajectories and mutational landscapes of drug-resistant bacteria are influenced by cell-intrinsic and extrinsic factors. In this study, I demonstrated that loss of the Lon protease altered susceptibility of Escherichia coli to trimethoprim and that these effects were strongly contingent on the drug concentration and genetic background. Lon, an AAA+ ATPase, is a bacterial master regulator protease involved in cytokinesis, suppression of transposition events, and clearance of misfolded proteins. I show that Lon deficiency enhances intrinsic drug tolerance at sub-MIC levels of trimethoprim. As a result, loss of Lon, though disadvantageous under drug-free conditions, has a selective advantage at low concentrations of trimethoprim. At high drug concentrations, however, Lon deficiency is detrimental for E. coli I show that the former is explained by suppression of drug efflux by Lon, while the latter can be attributed to SulA-dependent hyperfilamentation. On the other hand, deletion of lon in a trimethoprim-resistant mutant E. coli strain (harboring the Trp30Gly dihydrofolate reductase [DHFR] allele) directly potentiates resistance by enhancing the in vivo stability of mutant DHFR. Using extensive mutational analysis at 3 hot spots of resistance, I show that many resistance-conferring mutations render DHFR prone to proteolysis. This trade-off between gaining resistance and losing in vivo stability limits the number of mutations in DHFR that can confer trimethoprim resistance. Loss of Lon expands the mutational capacity for acquisition of trimethoprim resistance. This paper identifies the multipronged action of Lon in trimethoprim resistance in E. coli and provides mechanistic insight into how genetic backgrounds and drug concentrations may alter the potential for antimicrobial resistance evolution.IMPORTANCE Understanding the evolutionary dynamics of antimicrobial resistance is vital to curb its emergence and spread. Being fundamentally similar to natural selection, the fitness of resistant mutants is a key parameter to consider in the evolutionary dynamics of antimicrobial resistance (AMR). Various intrinsic and extrinsic factors modulate the fitness of resistant bacteria. This study demonstrated that Lon, a bacterial master regulator protease, influences drug tolerance and resistance. Lon is a key regulator of several fundamental processes in bacteria, including cytokinesis. I demonstrated that Lon deficiency produces highly contingent phenotypes in E. coli challenged with trimethoprim and can expand the mutational repertoire available to E. coli to evolve resistance. This multipronged influence of Lon on drug resistance provides an illustrative instance of how master regulators shape the response of bacteria to antibiotics.
journal_name
J Bacterioljournal_title
Journal of bacteriologyauthors
Matange Ndoi
10.1128/JB.00561-19subject
Has Abstractpub_date
2020-01-15 00:00:00issue
3eissn
0021-9193issn
1098-5530pii
JB.00561-19journal_volume
202pub_type
杂志文章abstract::Elongation factor P (EF-P) facilitates the translation of certain peptide motifs, including those with multiple proline residues. EF-P must be posttranslationally modified for full functionality; in enterobacteria, this is accomplished by two enzymes, namely, EpmA and EpmB, which catalyze the β-lysylation of EF-P at a...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00722-18
更新日期:2019-05-08 00:00:00
abstract::A second cluster of genes encoding the E1 alpha, E1 beta, and E2 subunits of branched-chain alpha-keto acid dehydrogenase (BCDH), bkdFGH, has been cloned and characterized from Streptomyces avermitilis, the soil microorganism which produces anthelmintic avermectins. Open reading frame 1 (ORF1) (bkdF, encoding E1 alpha...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.177.12.3504-3511.1995
更新日期:1995-06-01 00:00:00
abstract::Streptococcus pyogenes (group A streptococcus [GAS]), a catalase-negative gram-positive bacterium, is aerotolerant and survives H2O2 exposures that kill many catalase-positive bacteria. The molecular basis of the H2O2 resistance is poorly known. Here, we demonstrate that serotype M49 GAS lacking the Rgg regulator is m...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.01843-07
更新日期:2008-05-01 00:00:00
abstract::Quorum sensing is involved in the regulation of multicellular behavior through communication via small molecules. Given the high number and diversity of the gastrointestinal microbiota, it is postulated that members of this community communicate to coordinate a variety of adaptive processes. AI-2 is suggested to be a ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.01394-06
更新日期:2007-02-01 00:00:00
abstract::When dl-isoleucine was added to an ammonium nitrate-maltose medium during cultivation of Streptomyces sp. 732, quinomycin B formation was selectively enhanced (from 3 to 70% of the quinomycin mixture) and quinomycin C synthesis was inhibited completely. In addition, two new quinomycins, designated quinomycins D and E,...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.93.4.1327-1331.1967
更新日期:1967-04-01 00:00:00
abstract::Enhancement of the production of soluble recombinant penicillin acylase in Escherichia coli via coexpression of a periplasmic protease/chaperone, DegP, was demonstrated. Coexpression of DegP resulted in a shift of in vivo penicillin acylase (PAC) synthesis flux from the nonproductive pathway to the productive one when...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.185.10.3020-3030.2003
更新日期:2003-05-01 00:00:00
abstract::The chromatophores of Chromatium vinosum, as well as six other photosynthetic bacteria, contained two or more proteins which were insoluble when heated in the presence of sodium dodecyl sulfate (SDS) and 2-mercaptoethanol (beta-ME). When the chromatophores were dissolved at room temperature in SDS-beta-ME, these prote...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.138.1.207-217.1979
更新日期:1979-04-01 00:00:00
abstract::A Bacillus subtilis secA mutant, secA12, which is blocked at an early stage of sporulation, is able to grow as well as the wild-type strain at all temperatures tested. Experiments with lacZ fusion genes showed that the induction of kinA expression, as well as the sporulation-specific transcription of the spo0A gene, w...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.179.2.544-547.1997
更新日期:1997-01-01 00:00:00
abstract::Alginates are polysaccharides composed of 1-4-linked beta-D-mannuronic acid and alpha-L-guluronic acid. The polymer can be degraded by alginate lyases, which cleave the polysaccharide using a beta-elimination reaction. Two such lyases have previously been identified in the soil bacterium Azotobacter vinelandii, as fol...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00455-09
更新日期:2009-08-01 00:00:00
abstract::FpvR is a presumed cytoplasmic membrane-associated anti-sigma factor that controls the activities of extracytoplasmic function sigma factors PvdS and FpvI responsible for transcription of pyoverdine biosynthetic genes and the ferric pyoverdine receptor gene, fpvA, respectively. Using deletion analysis and an in vivo b...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.187.16.5648-5657.2005
更新日期:2005-08-01 00:00:00
abstract::The actinomycin synthetases ACMS I, II, and III catalyze the assembly of the acyl peptide lactone precursor of actinomycin by a nonribosomal mechanism. We have cloned the genes of ACMS I (acmA) and ACMS II (acmB) by hybridization screening of a cosmid library of Streptomyces chrysomallus DNA with synthetic oligonucleo...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.180.9.2468-2474.1998
更新日期:1998-05-01 00:00:00
abstract::A psychrotolerant marine bacterial strain, designated JUB59(T), was isolated from Antarctic surface seawater and classified as a new species of the genus Bizionia. Here, we present the first draft genome sequence for this genus, which suggests interesting features such as UV resistance, hydrolytic exoenzymes, and nitr...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.06245-11
更新日期:2011-12-01 00:00:00
abstract::Streptococcus pseudopneumoniae is a member of the viridans group streptococci (VGS) whose pathogenic significance is unclear. We announce the complete genome sequence of S. pseudopneumoniae IS7493. The genome sequence will assist in the characterization of this new organism and facilitate the development of accurate d...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.06075-11
更新日期:2011-11-01 00:00:00
abstract::The inducible galactose transport system in bakers' yeast carries out the facilitated diffusion of the nonmetabolized galactose analogues d-fucose and l-arabinose. This capacity depends on the activity of the Ga 2 gene. In some strains, d-fucose and l-arabinose are also gratuitous inducers. Mutants in which the induci...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.95.5.1727-1731.1968
更新日期:1968-05-01 00:00:00
abstract::In stationary phase, 95% of the fructosyltransferase (FTase) activity of Streptococcus salivarius ATCC 25975 was found associated with the cells. Within the first 15 min after inoculation into fresh medium, the specific activity of cell-associated FTase decreased by 92% of its initial value. After this period of initi...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.148.3.912-918.1981
更新日期:1981-12-01 00:00:00
abstract::Growth of Streptomyces viridochromogenes on a solid glycerol-NH4NO3 salts medium was accompanied by the formation of aerial mycelia and spores. Adding 0.5% or more casein hydrolysate to the medium stimulated growth while completely repressing the formation of aerial mycelia and spores. This repression was temporary, a...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.149.3.1102-1111.1982
更新日期:1982-03-01 00:00:00
abstract::The smallest viable cell of Spiroplasma citri is a two-turn helix (elementary helix). This elementary helix grows into longer parental cells, which then divide by constriction. The helical morphology is conserved during this process. The growth pattern of S. citri membranes has been investigated by different methods o...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.158.1.23-28.1984
更新日期:1984-04-01 00:00:00
abstract::In Mexico, actinomycetoma is mainly caused by Nocardia brasiliensis, which is a soil inhabitant actinobacterium. Here, we report for the first time the draft genome of a strain isolated from a human case that has largely been found in in vitro and experimental models of actinomycetoma, N. brasiliensis HUJEG-1. ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00210-12
更新日期:2012-05-01 00:00:00
abstract::Covalently closed circular deoxyribonucleic acid (DNA) was isolated from two strains of Streptomyces coelicolor A3(2), representing two of the known fertility types. In each of the two strains circular DNA of about 20 times 10-6 daltons could be detected, amounting to about 1.5% of the total cellular DNA. The possible...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.121.2.416-421.1975
更新日期:1975-02-01 00:00:00
abstract::The β-barrel assembly machinery (BAM) complex is the core machinery for the assembly of β-barrel membrane proteins, and inhibition of BAM complex activity is lethal to bacteria. Discovery of integral membrane proteins that are key to pathogenesis and yet do not require assistance from the BAM complex raises the questi...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00521-17
更新日期:2018-02-07 00:00:00
abstract::Azotobacter vinelandii was grown diazotrophically in chemostat cultures limited by sucrose, citrate, or acetate. Specific activities of cellular oxygen consumption (qO2) and nitrogenase (acetylene reduction) were measured in situ at different dilution rates (D, representing the specific growth rate mu at steady state)...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.170.11.5325-5329.1988
更新日期:1988-11-01 00:00:00
abstract::Isolated cell envelopes of a marine bacterium, M.B.3, have been prepared which possess a nonspecific, cation-activated nucleotidase. The cell envelope comprises approximately 35% (dry weight) of the whole cell and contains protein, 60.2%; lipids, 20.7%; hexose, 3.4%; and ribonucleic acid, 4.6%. No deoxyribonucleic aci...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.99.3.834-841.1969
更新日期:1969-09-01 00:00:00
abstract::Seventeen strains of mycoplasmata representing 11 named species were compared serologically by three parameters: growth inhibition on agar, double immunodiffusion, and complement fixation. In growth-inhibition studies, a strain labeled Mycoplasma histotropicum was found related to and perhaps best classified as M. pul...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.98.3.1044-1055.1969
更新日期:1969-06-01 00:00:00
abstract::Phospholipid synthesis has been reported to be subject to stringent control in Escherichia coli. We present evidence that demonstrates a strict correlation between guanosine tetraphosphate accumulation and inhibition of phospholipid synthesis. In vivo experiments designed to examine the pattern of phospholipid labelin...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.116.1.355-366.1973
更新日期:1973-10-01 00:00:00
abstract::Using a system of chromatography through columns of DEAE-Bio-Gel, HTP-Bio-Gel, and CM-Bio-Gel, we isolated and characterized six different (1 leads to 3)-beta-glucanases from cell wall autolysates and cell extracts of Saccharomyces cerevisiae haploid strain 2180B. These enzymes were designated glucanases I, II, IIIA, ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.156.3.1204-1213.1983
更新日期:1983-12-01 00:00:00
abstract::The endophytic diazotroph Azoarcus sp. strain BH72 is capable of infecting rice roots and of expressing the nitrogenase (nif) genes there. In order to study the genetic background for nitrogen fixation in strain BH72, the structural genes of nitrogenase (nifHDK) were cloned and sequenced. The sequence analysis reveale...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.183.12.3752-3760.2001
更新日期:2001-06-01 00:00:00
abstract::When Azotobacter vinelandii was derepressed for nitrogenase synthesis in a N-free medium containing tungstate instead of molybdate, an inactive component I was synthesized. Although this inactive component I could be activated in vivo upon addition of molybdate to the medium, it could not be activated in vitro when mo...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.120.2.697-701.1974
更新日期:1974-11-01 00:00:00
abstract::The extent of change in cytoplasmic proteins which accompanies yeast-to-mycelium morphogenesis of Candida albicans was analyzed by two-dimensional gel electrophoresis. Pure cultures of yeasts and true hyphae (i.e., without concomitant production of pseudohyphae) were grown in a synthetic low-sulfate medium. The two st...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.144.1.258-273.1980
更新日期:1980-10-01 00:00:00
abstract::Accumulation of l-alpha-glycerophosphate, in cells of Bacillus subtilis mutants lacking the nicotinamide adenine dinucleotide-independent glycerophosphate dehydrogenase activity, suppresses both growth and sporulation. After growth has stopped, the cells slowly develop one and later more asymmetric septa that are thic...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.113.2.1034-1045.1973
更新日期:1973-02-01 00:00:00
abstract::The direction of chromosome replication in a temperature-sensitive initiation mutant of Escherichia coli (CT28) is shown autoradiographically to be bidirectional. This mode of replication persists even when the rate of replication is reduced by slow growth in succinate minimal medium or in the presence of chlorampheni...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.125.1.346-352.1976
更新日期:1976-01-01 00:00:00