Abstract:
:Antibiotic-resistant Acinetobacter baumannii causes infections that are extremely difficult to treat. A significant role in these resistance profiles is attributed to multidrug efflux pumps, especially those belonging to the resistance-nodulation-cell division (RND) superfamily of transporters. In this study, we analyzed functions and properties of RND efflux pumps in A. baumannii ATCC 17978. This strain is susceptible to antibiotics and does not contain mutations that are commonly selected upon exposure to high concentrations of antibiotics. We constructed derivatives of ATCC 17978 lacking chromosomally encoded RND pumps and complemented these strains by the plasmid-borne genes. We analyzed the substrate selectivities and efficiencies of the individual pumps in the context of native outer membranes and their hyperporinated variants. Our results show that inactivation of AdeIJK provides the strongest potentiation of antibiotic activities, whereas inactivation of AdeFGH triggers the overexpression of AdeAB. The plasmid-borne overproduction complements the hypersusceptible phenotypes of the efflux deletion mutants to the levels of the parental ATCC 17978. Only a few antibiotics strongly benefitted from the overproduction of efflux pumps and antibacterial activities of some of those depended on the synergistic interaction with the low permeability barrier of the outer membrane. Either overproduction or inactivation of efflux pumps change dramatically the lipidome of ATCC 17978. We conclude that efflux pumps of A. baumannii are tightly integrated into physiology of this bacterium and that clinical levels of antibiotic resistance in A. baumannii isolates are unlikely to be reached solely due to the overproduction of RND efflux pumps.IMPORTANCE RND-type efflux pumps are important contributors in development of clinical antibiotic resistance in A. baumannii However, their specific roles and the extent of contribution to antibiotic resistance remain unclear. We analyzed antibacterial activities of antibiotics in strains with different permeability barriers and found that the role of active efflux in antibiotic resistance of A. baumannii is limited to a few select antibiotics. Our results further show that the impact of efflux pump overproduction on antibiotic susceptibility is significantly lower than the previously reported for clinical isolates. Additional mechanisms of resistance, in particular those that improve the permeability barriers of bacterial cells and act synergistically with active efflux pumps are likely involved in antibiotic resistance of clinical A. baumannii isolates.
journal_name
J Bacterioljournal_title
Journal of bacteriologyauthors
Leus IV,Weeks JW,Bonifay V,Smith L,Richardson S,Zgurskaya HIdoi
10.1128/JB.00049-18subject
Has Abstractpub_date
2018-06-11 00:00:00issue
13eissn
0021-9193issn
1098-5530pii
JB.00049-18journal_volume
200pub_type
杂志文章abstract::The isolation and some properties of two mutants of Streptococcus faecalis ATCC 9790 (S. faecium) which autolyze at a much slower rate than the wild type are described. Compared with the wild type, mutant E71 autolyzed more slowly, contained less active but more latent autolysin in the isolated wall fraction, and poss...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.109.1.423-431.1972
更新日期:1972-01-01 00:00:00
abstract::Agrobacterium tumefaciens and Rhizobium meliloti carry related genetic loci which have important roles in virulence and symbiosis. Previously, it was shown that two virulence loci of A. tumefaciens, chvA and chvB, are related to two R. meliloti symbiosis loci, ndvA and ndvB, respectively (T. Dylan, L. Ielpi, S. Stanfi...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.169.12.5835-5837.1987
更新日期:1987-12-01 00:00:00
abstract::Campylobacter jejuni 81-176 lipooligosaccharide (LOS) is composed of two covalently linked domains: lipid A, a hydrophobic anchor, and a nonrepeating core oligosaccharide, consisting of an inner and outer core region. We report the isolation and characterization of the deepest rough C. jejuni 81-176 mutant by insertio...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.188.9.3273-3279.2006
更新日期:2006-05-01 00:00:00
abstract::The dermatophyte Trichophyton schoenleinii elaborates an extracellular collagenase which is specific for native collagen and gelatin and is separable from an enzyme which is active against Azocoll. The fungal enzyme differs from the bacterial collagenases in its acid pH and small molecular weight. In addition, the fun...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.95.1.43-46.1968
更新日期:1968-01-01 00:00:00
abstract::Maleylacetate reductase (EC 1.3.1.32) plays a major role in the degradation of chloroaromatic compounds by channelling maleylacetate and some chlorinated derivatives into the 3-oxoadipate pathway. Several substituted maleylacetates were prepared in situ by alkaline or enzymatic hydrolysis of dienelactones as the precu...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.177.2.320-325.1995
更新日期:1995-01-01 00:00:00
abstract::Mycoplasma pneumoniae harvested from media which had become acid lost the ability both to induce formation of tetrazolium reduction inhibition antibody and to act as antigens in immunodiffusion against human convalescent-phase sera. Incorporation of N-tris(hydroxymethyl)-2-aminoethane sulfonic acid and N-2-hydroxyethy...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.97.2.612-619.1969
更新日期:1969-02-01 00:00:00
abstract::Coat-stripped spores suspended in hypertonic solutions and supplied with two essential cations can be converted into viable protoplasts by lysozyme digestion of both cortex and germ cell wall. Calcium ions are necessary to prevent membrane rupture, and magnesium ions are necessary for changes indicative of hydration o...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.105.3.1119-1136.1971
更新日期:1971-03-01 00:00:00
abstract::Flac mutants insensitive to transfer inhibition by R factors. JR66a and R485 were isolated and characterized. Representative mutations were cis dominant and are therefore presumed to be at the sites of action, fisU and fisV, respectively, of the FinU and FinV transfer inhibition systems encoded by JR66a and R485. The ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.131.2.413-420.1977
更新日期:1977-08-01 00:00:00
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journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.182.13.3661-3672.2000
更新日期:2000-07-01 00:00:00
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journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.187.23.8172-8180.2005
更新日期:2005-12-01 00:00:00
abstract::The hexose phosphate transport system transported glycerol 3-phosphate and its analogs 3,4-dihydroxybutyl-1-phosphonate, glyceraldehyde 3-phosphate, and 3-hydroxy-4-oxobutyl-1-phosphonate. ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.143.1.538-539.1980
更新日期:1980-07-01 00:00:00
abstract::The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward gram-positive bacteria. A screen of fatty acids as growth inhibitors of Staphylococcus aureus revealed structure-specific antibacterial activity. Fatty acids like oleate (18:1Δ9) were nontoxic, whereas palm...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00743-12
更新日期:2012-10-01 00:00:00
abstract::The biodegradative threonine dehydratase (tdc) operon was mapped at 68 min on the Escherichia coli K-12 chromosome. The order of markers in the clockwise direction was dnaG uxaA tdc argG. A tdc deletion was isolated and mapped to this region of the chromosome. By using a tdcB-lacZ fusion the clockwise direction of tra...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.170.11.5360-5363.1988
更新日期:1988-11-01 00:00:00
abstract::Cultures of a stable L-phase variant of Streptococcus faecium F24 produced and retained peptidoglycan precursors intracellularly over the entire growth cycle in a chemically defined medium. The identity of the most abundant precursor, UDP N-acetylmuramyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine (UDP-MurNAc-penta...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.135.3.900-910.1978
更新日期:1978-09-01 00:00:00
abstract::The Klebsiella aerogenes hutUH operon is preceded by a promoter region, hut(P), that contains two divergent promoters (hutUp and Pc) which overlap and are alternately expressed. In the absence of the catabolite gene activator protein-cyclic AMP (CAP-cAMP) complex, Pc is predominantly expressed while hutUp is largely r...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.176.17.5513-5524.1994
更新日期:1994-09-01 00:00:00
abstract::The tdh promoter of Escherichia coli is induced seven- to eightfold when cells are grown in the presence of exogenous leucine. A scheme was devised to select mutants that exhibited high constitutive expression of the tdh promoter. The mutations in these strains were shown to lie within a previously identified gene (lr...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.173.19.5944-5953.1991
更新日期:1991-10-01 00:00:00
abstract::We used primer extension and mutational analysis to identify a promoter upstream of ilvB, the first gene in the ilv-leu operon of Bacillus subtilis. Between the promoter and ilvB, there is a 482-bp leader region which contains a sequence that resembles a factor-independent transcription terminator. In in vitro transcr...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.174.10.3212-3219.1992
更新日期:1992-05-01 00:00:00
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journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.100.1.103-109.1969
更新日期:1969-10-01 00:00:00
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journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.145.1.548-558.1981
更新日期:1981-01-01 00:00:00
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journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.179.12.3858-3865.1997
更新日期:1997-06-01 00:00:00
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journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00585-09
更新日期:2009-09-01 00:00:00
abstract::Divercin V41, a class IIa bacteriocin with strong antilisterial activity, is produced by Carnobacterium divergens V41. To express a recombinant version of divercin V41, we constructed a synthetic gene that encodes the mature divercin V41 peptide and then overexpressed the gene in pET-32b by using the T7 RNA polymerase...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.186.13.4276-4284.2004
更新日期:2004-07-01 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::Dental plaque is a complex biofilm that accretes in a series of discrete steps proceeding from a gram-positive streptococcus-rich biofilm to a structure rich in gram-negative anaerobes. This study investigated information flow between two unrelated plaque bacteria, Streptococcus cristatus and Porphyromonas gingivalis....
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.182.24.7067-7069.2000
更新日期:2000-12-01 00:00:00
abstract::A polA12 recA718 double mutant of Escherichia coli, in which DNA polymerase I is temperature sensitive, was unable to maintain normal DNA synthesis or to form colonies on rich media at 42 degrees C. Overproduction of DnaE protein, the polymerizing alpha subunit of DNA polymerase III, restored bacterial DNA replication...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.174.12.4166-4168.1992
更新日期:1992-06-01 00:00:00
abstract::The number of rRNA genes in Mycobacterium bovis BCG was examined by Southern hybridization of end-labeled 5S, 16S, and 23S rRNAs with BamHI, PstI, and SalI digests of M. bovis BCG DNA. Each RNA probe gave only one radioactive band with three kinds of DNA digest. These results suggest that M. bovis BCG chromosomes may ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.169.2.839-843.1987
更新日期:1987-02-01 00:00:00
abstract::Burkholderia species, including opportunistic pathogens in the Burkholderia cepacia complex (Bcc), have genes to produce contact-dependent growth inhibition (CDI) system proteins. CDI is a phenomenon in which Gram-negative bacteria use the toxic C terminus of a polymorphic surface-exposed exoprotein, BcpA, to inhibit ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00012-19
更新日期:2019-05-22 00:00:00
abstract::Clostridium perfringens type B and D isolates produce epsilon-toxin, the third most potent clostridial toxin. The epsilon-toxin gene (etx) is plasmid borne in type D isolates, but etx genetics have been poorly studied in type B isolates. This study reports the first sequencing of any etx plasmid, i.e., pCP8533etx, fro...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00939-08
更新日期:2008-11-01 00:00:00
abstract::Biodegradation of metal-citrate complexes by Pseudomonas fluorescens depends on the nature of the complex formed between the metal and citric acid. Bidentate Fe(III)-, Ni-, and Zn-citrate complexes were readily biodegraded, but the tridentate Cd- and Cu-citrate, and U-citrate complexes were not. The biodegradation of ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.177.8.1989-1993.1995
更新日期:1995-04-01 00:00:00
abstract::The antibiotic albomycin is highly effective against Streptococcus pneumoniae, with an MIC of 10 ng/ml. The reason for the high efficacy was studied by measuring the uptake of albomycin into S. pneumoniae. Albomycin was transported via the system that transports the ferric hydroxamates ferrichrome and ferrioxamine B. ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00205-06
更新日期:2006-06-01 00:00:00