Lon protease inactivation, or translocation of the lon gene, potentiate bacterial evolution to antibiotic resistance.

Abstract:

:Previous work demonstrated that selection for Escherichia coli mutants with low antibiotic resistance frequently resulted in co-selection of lon mutations and that lon(-) mutants evolved higher-level resistance faster than a lon(+) strain. Here we show that lon mutation causes a very low multidrug resistance by inducing the AcrAB-TolC pump via stabilization of the acrAB transcriptional activators MarA and SoxS, which are substrates of the Lon protease. Fast evolution of lon(-) mutants towards higher resistance involves selection of frequent next-step mutations consisting of large duplications including acrAB and the mutated lon gene. Resistance results from the combined effects of acrAB duplication and lon mutation increasing dosage of efflux pump. In contrast, when acrAB duplication occurs as the first step mutation, increased Lon activity caused by lon(+) co-duplication mitigates the effect of acrAB duplication on resistance, and faster evolution towards higher resistance is not observed. As predicted, when the functional lon gene is relocated far from acrAB to prevent their co-duplication, first-step acrAB duplication confers higher resistance, which then allows selection of frequent next-step mutations and results in faster evolution towards higher resistance. Our results demonstrate how order of appearance of mutations and gene location can influence the rate of resistance evolution.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Nicoloff H,Andersson DI

doi

10.1111/mmi.12429

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

1233-48

issue

6

eissn

0950-382X

issn

1365-2958

journal_volume

90

pub_type

杂志文章
  • A new component of bacteriophage Mu replicative transposition machinery: the Escherichia coli ClpX protein.

    abstract::We have shown previously that some particular mutations in bacteriophage Mu repressor, the frameshift vir mutations, made the protein very sensitive to the Escherichia coli ATP-dependent Clp protease. This enzyme is formed by the association between a protease subunit (ClpP) and an ATPase subunit. ClpA, the best chara...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb00387.x

    authors: Mhammedi-Alaoui A,Pato M,Gama MJ,Toussaint A

    更新日期:1994-03-01 00:00:00

  • The non-ribosomal assembly and frequent occurrence of the protease inhibitors spumigins in the bloom-forming cyanobacterium Nodularia spumigena.

    abstract::Nodularia spumigena is a filamentous nitrogen-fixing cyanobacterium that forms toxic blooms in brackish water bodies worldwide. Spumigins are serine protease inhibitors reported from a single strain of N. spumigena isolated from the Baltic Sea. These linear tetrapeptides contain non-proteinogenic amino acids including...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06816.x

    authors: Fewer DP,Jokela J,Rouhiainen L,Wahlsten M,Koskenniemi K,Stal LJ,Sivonen K

    更新日期:2009-09-01 00:00:00

  • A haem cofactor is required for redox and light signalling by the AppA protein of Rhodobacter sphaeroides.

    abstract::The AppA protein of Rhodobacter sphaeroides is unique in its ability to sense and transmit redox signals as well as light signals. By functioning as antagonist to the PpsR transcriptional repressor, it regulates the expression of photosynthesis genes in response to these environmental stimuli. Here we show binding of ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2007.05724.x

    authors: Han Y,Meyer MH,Keusgen M,Klug G

    更新日期:2007-05-01 00:00:00

  • Autoregulation of the Escherichia coli replication initiator protein, DnaA, is indirect.

    abstract::The expression of dnaA is autoregulated, in that transcription of the gene increases when DnaA is inactivated (and initiation of replication prevented) and decreases when DnaA is supplied in excess. However, the inactivation of DnaA does not necessarily lead to increased DnaA production, as dnaA(Ts; temperature sensit...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1997.3121675.x

    authors: Smith RW,McAteer S,Masters M

    更新日期:1997-03-01 00:00:00

  • Pentapeptide-rich peptidoglycan at the Bacillus subtilis cell-division site.

    abstract::Peptidoglycan (PG), the major component of the bacterial cell wall, is one large macromolecule. To allow for the different curvatures of PG at cell poles and division sites, there must be local differences in PG architecture and eventually also chemistry. Here we report such local differences in the Gram-positive rod-...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13629

    authors: Morales Angeles D,Liu Y,Hartman AM,Borisova M,de Sousa Borges A,de Kok N,Beilharz K,Veening JW,Mayer C,Hirsch AK,Scheffers DJ

    更新日期:2017-04-01 00:00:00

  • Biofilm formation at the air-liquid interface by the Pseudomonas fluorescens SBW25 wrinkly spreader requires an acetylated form of cellulose.

    abstract::The wrinkly spreader (WS) genotype of Pseudomonas fluorescens SBW25 colonizes the air-liquid interface of spatially structured microcosms resulting in formation of a thick biofilm. Its ability to colonize this niche is largely due to overproduction of a cellulosic polymer, the product of the wss operon. Chemical analy...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03670.x

    authors: Spiers AJ,Bohannon J,Gehrig SM,Rainey PB

    更新日期:2003-10-01 00:00:00

  • The chemosensory systems of Vibrio cholerae.

    abstract::Vibrio cholerae, the causative agent of the acute diarrheal disease cholera, is able to thrive in diverse habitats such as natural water bodies and inside human hosts. To ensure their survival, these bacteria rely on chemosensory pathways to sense and respond to changing environmental conditions. These pathways consti...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/mmi.14520

    authors: Ortega DR,Kjaer A,Briegel A

    更新日期:2020-09-01 00:00:00

  • Activator-independent formation of a closed complex between sigma 54-holoenzyme and nifH and nifU promoters of Klebsiella pneumoniae.

    abstract::The alternative sigma factor sigma 54 is required for transcription of nitrogen fixation genes in Klebsiella pneumoniae and other diazotrophs. The nif genes, and other E sigma 54-dependent genes whose products are necessary for a wide range of processes, are postively regulated. A unifying model that is well supported...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1992.tb00887.x

    authors: Buck M,Cannon W

    更新日期:1992-06-01 00:00:00

  • Reduced polysialic acid capsule expression in Escherichia coli K1 mutants with chromosomal defects in kpsF.

    abstract::Neuroinvasive Escherichia coli K1 synthesizes and assembles a polysialic acid capsule virulence factor on the external leaflet of the outer membrane. This capsule functions in pathogenesis by blocking non-immune host defence mechanisms and acting as a relatively non-immunogenic molecular mimic of the polysialic acid c...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1997.5651942.x

    authors: Cieslewicz M,Vimr E

    更新日期:1997-10-01 00:00:00

  • The putative invasion protein chaperone SicA acts together with InvF to activate the expression of Salmonella typhimurium virulence genes.

    abstract::SigD and SigE (Salmonella invasion gene) are proteins needed for optimal invasion of Salmonella typhimurium into eukaryotic cells in vitro. SigD is a secreted protein and SigE is a putative chaperone required for SigD stability and/or secretion. SigD is secreted by a type III secretion apparatus encoded within a patho...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2000.01772.x

    authors: Darwin KH,Miller VL

    更新日期:2000-02-01 00:00:00

  • Agents of change - concepts in Mycobacterium tuberculosis Ser/Thr/Tyr phosphosignalling.

    abstract::The flow of information from the outside to the inside of bacterial cells is largely directed by protein kinases. In addition to histidine/aspartate phosphorelays of two-component response regulators, recent work in Mycobacterium tuberculosis (Mtb) reinforces the idea that phosphorylation on serine (Ser), threonine (T...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/mmi.12747

    authors: Sherman DR,Grundner C

    更新日期:2014-10-01 00:00:00

  • Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.

    abstract::Calcineurin plays essential roles in virulence and growth of pathogenic fungi and is a target of the natural products FK506 and Cyclosporine A. In the pathogenic mucoralean fungus Mucor circinelloides, calcineurin mutation or inhibition confers a yeast-locked phenotype indicating that calcineurin governs the dimorphic...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13071

    authors: Lee SC,Li A,Calo S,Inoue M,Tonthat NK,Bain JM,Louw J,Shinohara ML,Erwig LP,Schumacher MA,Ko DC,Heitman J

    更新日期:2015-09-01 00:00:00

  • Biosynthesis of mycobacterial arabinogalactan: identification of a novel alpha(1-->3) arabinofuranosyltransferase.

    abstract::The cell wall mycolyl-arabinogalactan-peptidoglycan complex is essential in mycobacterial species, such as Mycobacterium tuberculosis and is the target of several antitubercular drugs. For instance, ethambutol targets arabinogalactan biosynthesis through inhibition of the arabinofuranosyltransferases Mt-EmbA and Mt-Em...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2008.06354.x

    authors: Birch HL,Alderwick LJ,Bhatt A,Rittmann D,Krumbach K,Singh A,Bai Y,Lowary TL,Eggeling L,Besra GS

    更新日期:2008-09-01 00:00:00

  • Organization and regulation of the Corynebacterium glutamicum hom-thrB and thrC loci.

    abstract::The genes encoding the three terminal enzymes in the threonine biosynthetic pathway, homoserine dehydrogenase (hom), homoserine kinase (thrB) and threonine synthase (thrC) have been isolated from Corynebacterium glutamicum. The C. glutamicum hom and thrB genes were subcloned on a 3.6 kb SalI-generated chromosomal frag...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1988.tb00006.x

    authors: Follettie MT,Shin HK,Sinskey AJ

    更新日期:1988-01-01 00:00:00

  • Constraints in chromosomal inversions in Escherichia coli are not explained by replication pausing at inverted terminator-like sequences.

    abstract::Regions close to the replication terminus of the Escherichia coli chromosome are strongly refractory to genomic inversions. Since these regions also harbour polar replication terminator-like sequences or pause sites, we have investigated the possibility that slowing of replication as a result of pausing at inverted pa...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1990.tb00621.x

    authors: François V,Louarn J,Patte J,Rebollo JE,Louarn JM

    更新日期:1990-04-01 00:00:00

  • The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals.

    abstract::Genes acrAB encode a multidrug efflux pump in Escherichia coli. We have previously reported that transcription of acrAB is increased under general stress conditions (i.e. 4% ethanol, 0.5 M NaCl, and the stationary phase in Luria-Bertani medium). In this study, lacZ transcriptional fusions and an in vitro gel mobility ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1996.357881.x

    authors: Ma D,Alberti M,Lynch C,Nikaido H,Hearst JE

    更新日期:1996-01-01 00:00:00

  • Novel coordination of lipopolysaccharide modifications in Vibrio cholerae promotes CAMP resistance.

    abstract::In the environment and during infection, the human intestinal pathogen Vibrio cholerae must overcome noxious compounds that damage the bacterial outer membrane. The El Tor and classical biotypes of O1 V. cholerae show striking differences in their resistance to membrane disrupting cationic antimicrobial peptides (CAMP...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13835

    authors: Herrera CM,Henderson JC,Crofts AA,Trent MS

    更新日期:2017-11-01 00:00:00

  • Selective expression of the beta-subunit of nucleoid-associated protein HU during cold shock in Escherichia coli.

    abstract::Expression of Escherichia coli hupA and hupB, the structural genes encoding the most abundant nucleoid-associated proteins HUalpha and HUbeta has been studied during cold shock. This article demonstrates that: (i) transcriptional expression of hupA is blocked following a sudden temperature downshift (from 37 degrees C...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.02868.x

    authors: Giangrossi M,Giuliodori AM,Gualerzi CO,Pon CL

    更新日期:2002-04-01 00:00:00

  • The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation.

    abstract::Molecular analyses were applied to the genes encoding variants of the serosubtyping antigen, the class 1 outer membrane protein (PorA), from 55 serogroup A Neisseria meningitidis strains. These genes were evolutionarily stable and exhibited a limited range of genetic variation, primarily generated by recombination. Tr...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb01014.x

    authors: Suker J,Feavers IM,Achtman M,Morelli G,Wang JF,Maiden MC

    更新日期:1994-04-01 00:00:00

  • Supercoiling of an excised genomic island represses effector gene expression to prevent activation of host resistance.

    abstract::The plant pathogen Pseudomonas syringae pv. phaseolicola, which causes halo blight disease of beans, contains a 106 kb genomic island PPHGI-1. PPHGI-1 carries a gene, avrPphB, which encodes an effector protein that triggers a resistance response in certain bean cultivars. Previous studies have shown that when PPHGI-1 ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.14111

    authors: Neale HC,Jackson RW,Preston GM,Arnold DL

    更新日期:2018-11-01 00:00:00

  • Generation of the heterodimeric precursor GP3 of the Chlamydomonas cell wall.

    abstract::The cell wall of the unicellular green alga Chlamydomonas reinhardtii exclusively consists of hydroxyproline-containing glycoproteins. Protein chemical analysis of its polypeptide constituents was hindered by their cross-linking via peroxidase-catalysed intermolecular isodityrosine formation and transaminase-dependent...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07302.x

    authors: Voigt J,Kiess M,Getzlaff R,Wöstemeyer J,Frank R

    更新日期:2010-09-01 00:00:00

  • Apoptosis of mouse dendritic cells is triggered by listeriolysin, the major virulence determinant of Listeria monocytogenes.

    abstract::Infection of a murine-spleen dendritic cell line by Listeria monocytogenes was found to induce cell death through apoptosis. To characterize the bacterial product(s) involved in induction of apoptosis, dendritic cells were infected with the L. monocytogenes EGD strain and several isogenic mutants deficient in the prod...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1996.tb02494.x

    authors: Guzmán CA,Domann E,Rohde M,Bruder D,Darji A,Weiss S,Wehland J,Chakraborty T,Timmis KN

    更新日期:1996-04-01 00:00:00

  • Analysis of the gene cluster involved in production and immunity of the peptide antibiotic AS-48 in Enterococcus faecalis.

    abstract::A region of 7.8 kb of the plasmid pMB2 from Enterococcus faecalis S-48 carrying the information necessary for production and immunity of the peptide antibiotic AS-48 has been cloned and sequenced. It contains the as-48A structural gene plus five open reading frames (as-48B, as-48C, as-48C1, as-48D and as-48D1). Beside...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1998.00682.x

    authors: Martínez-Bueno M,Valdivia E,Gálvez A,Coyette J,Maqueda M

    更新日期:1998-01-01 00:00:00

  • The two faces of ToxR: activator of ompU, co-regulator of toxT in Vibrio cholerae.

    abstract::ToxR of Vibrio cholerae directly activates the ompU promoter, but requires a second activator, TcpP to activate the toxT promoter. ompU encodes a porin, while toxT encodes the transcription factor, ToxT, which activates V. cholerae virulence genes including cholera toxin and the toxin co-regulated pilus. Using an ompU...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2011.07681.x

    authors: Morgan SJ,Felek S,Gadwal S,Koropatkin NM,Perry JW,Bryson AB,Krukonis ES

    更新日期:2011-07-01 00:00:00

  • Role of Escherichia coli FtsN protein in the assembly and stability of the cell division ring.

    abstract::Deprivation of FtsN, the last protein in the hierarchy of divisome assembly, causes the disassembly of other elements from the division ring, even extending to already assembled proto-ring proteins. Therefore the stability and function of the divisome to produce rings active in septation is not guaranteed until FtsN i...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07134.x

    authors: Rico AI,García-Ovalle M,Palacios P,Casanova M,Vicente M

    更新日期:2010-05-01 00:00:00

  • Functional analysis of the Bacillus subtilis morphogenetic spore coat protein CotE.

    abstract::Bacterial spores are surrounded by a multilayered proteinaceous shell called the coat. In Bacillus subtilis, a coat protein called CotE guides the assembly of a major subset of coat proteins. To understand how CotE carries out its role in coat morphogenesis, we subjected its gene to mutagenesis and studied the effects...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2001.02708.x

    authors: Little S,Driks A

    更新日期:2001-11-01 00:00:00

  • Determinants of the streptococcal surface glycoprotein GspB that facilitate export by the accessory Sec system.

    abstract::GspB is a large cell-surface glycoprotein expressed by Streptococcus gordonii M99 that mediates binding of this organism to human platelets. This adhesin is glycosylated in the cytoplasm, and is then transported to the cell surface via an accessory Sec system. To assess the structural features of GspB that are needed ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04919.x

    authors: Bensing BA,Takamatsu D,Sullam PM

    更新日期:2005-12-01 00:00:00

  • Mycobacterial protein antigens: a compilation.

    abstract::In response to recommendations from the Steering Committees responsible for co-ordination of World Health Organization programmes for research on the immunology of leprosy (IMMLEP) and tuberculosis (IMMTUB), a list was prepared summarizing the properties of mycobacterial proteins currently under investigation with res...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2958.1992.tb01994.x

    authors: Young DB,Kaufmann SH,Hermans PW,Thole JE

    更新日期:1992-01-01 00:00:00

  • Role of lipid modification on a starch-debranching enzyme, Klebsieila pullulanase: comparison of properties of lipid-modified and unmodified pullulanases.

    abstract::Klebsiella pullulanase is a lipoprotein synthesized as a precursor with a signal peptide, which is processed by lipoprotein signal peptidase. To clarify the role of lipid modification of pullulanase, we purified lipid-modified wild-type and the unmodified (mutant) pullulanases and compared their properties. The Km and...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1992.tb01482.x

    authors: Yamashita M,Nakagawa A,Katsuragi N,Murooka Y

    更新日期:1992-02-01 00:00:00

  • Lactococcus lactis YfiA is necessary and sufficient for ribosome dimerization.

    abstract::Dimerization and inactivation of ribosomes in Escherichia coli is a two-step process that involves the binding of ribosome modulation factor (RMF) and hibernation promotion factor (HPF). Lactococcus lactis MG1363 expresses a protein, YfiA(L) (l) , which associates with ribosomes in the stationary phase of growth and i...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12468

    authors: Puri P,Eckhardt TH,Franken LE,Fusetti F,Stuart MC,Boekema EJ,Kuipers OP,Kok J,Poolman B

    更新日期:2014-01-01 00:00:00