In vitro activities of piperacillin against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae.
AuthorsMorikawa Y, Kitazato M, Mitsuyama J, Mizunaga S, Minami S, Watanabe Y
JournalAntimicrob Agents Chemother
PubMed ID15047524
'The in vitro activities of piperacillin (PIP) against beta-lactamase-negative ampicillin (AMP)-resistant (BLNAR) Haemophilus influenzae were compared with those of cefotaxime (CTX) and ceftriaxone (CRO), and the potency of PIP as therapy for meningitis caused by BLNAR is also discussed. PIP showed good activity (MIC at which 90% of strains are ... More
Characterization of HMW-PBPs from the rod-shaped actinomycete Corynebacterium glutamicum: peptidoglycan synthesis in cells lacking actin-like cytoskeletal structures.
AuthorsValbuena N, Letek M, Ordóñez E, Ayala J, Daniel RA, Gil JA, Mateos LM,
JournalMol Microbiol
PubMed ID17877698
'Analysis of the complete genome sequence of Corynebacterium glutamicum indicated that, in addition to ftsI, there are eight proteins with sequence motifs that are strongly conserved in penicillin binding proteins (PBPs): four genes that code for high-molecular-weight (HMW)-PBPs (PBP1a, PBP1b, PBP2a and PBP2b), two genes encoding low-molecular-weight PBPs (PBP4 and ... More
Penicillin-binding protein 2a of Streptococcus pneumoniae: expression in Escherichia coli and purification and refolding of inclusion bodies into a soluble and enzymatically active enzyme.
AuthorsZhao G, Meier TI, Hoskins J, Jaskunas SR
JournalProtein Expr Purif
PubMed ID10419829
'Penicillin-binding proteins (PBPs), targets of beta-lactam antibiotics, are membrane-bound enzymes essential for the biosynthesis of the bacterial cell wall. PBPs possess transpeptidase and transglycosylase activities responsible for the final steps of the bacterial cell wall cross-linking and polymerization, respectively. To facilitate our structural studies of PBPs, we constructed a 5''-truncated ... More
The basis for resistance to beta-lactam antibiotics by penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus.
AuthorsFuda C, Suvorov M, Vakulenko SB, Mobashery S
JournalJ Biol Chem
PubMed ID15226303
'Penicillin-binding protein 2a (PBP2a) of Staphylococcus aureus is refractory to inhibition by available beta-lactam antibiotics, resulting in resistance to these antibiotics. The strains of S. aureus that have acquired the mecA gene for PBP2a are designated as methicillin-resistant S. aureus (MRSA). The mecA gene was cloned and expressed in Escherichia ... More
The cysteine-rich protein A from Helicobacter pylori is a beta-lactamase.
AuthorsMittl PR, Lüthy L, Hunziker P, Grütter MG
JournalJ Biol Chem
PubMed ID10748053
'Among the large number of hypothetical proteins within the genomes of Helicobacter pylori, there is a family of unique and highly disulfide-bridged proteins, designated family 12, for which no function could originally be assigned. Sequence analysis revealed that members of this family possess a modular architecture of alpha/beta-units and a ... More
A novel beta-lactamase activity from a penicillin-binding protein of Treponema pallidum and why syphilis is still treatable with penicillin.
AuthorsCha JY, Ishiwata A, Mobashery S
JournalJ Biol Chem
PubMed ID14747460
'Treponema pallidum, the causative agent of syphilis, is sensitive to penicillins. Yet, an abundant membrane-bound protein of this organism, Tp47, turns over penicillins. It is shown herein that the turnover process is a hydrolytic reaction that results in the corresponding penicilloates, products that have their beta-lactam bonds hydrolyzed. This is ... More
Resistance to beta-lactam antibiotics and its mediation by the sensor domain of the transmembrane BlaR signaling pathway in Staphylococcus aureus.
AuthorsGolemi-Kotra D, Cha JY, Meroueh SO, Vakulenko SB, Mobashery S
JournalJ Biol Chem
PubMed ID12591921
'Staphylococci, a leading cause of infections worldwide, have devised two mechanisms for resistance to beta-lactam antibiotics. One is production of beta-lactamases, hydrolytic resistance enzymes, and the other is the expression of penicillin-binding protein 2a (PBP 2a), which is not susceptible to inhibition by beta-lactam antibiotics. The beta-lactam sensor-transducer (BlaR), an ... More
Heterogeneity of methicillin-resistant Staphylococcus aureus strains (MRSA) characterized by flow cytometry.
AuthorsJarzembowski T, Wisniewska K, Józwik A, Witkowski J,
JournalCurr Microbiol
PubMed ID19330377
'We used fluorescent penicillin Bocillin FL for characterization of control methicillin-resistant Staphylococcus aureus (MRSA) strains belonging to one of four heterogenic classes and comparing them with clinical MRSA isolates. Significant differences in percentage of fluorescent cells and reduction of Bocillin FL binding after incubation with methicillin between control strains from ... More
Reactions of peptidoglycan-mimetic beta-lactams with penicillin-binding proteins in vivo and in membranes.
AuthorsKumar I, Josephine HR, Pratt RF,
JournalACS Chem Biol
PubMed ID17894439
'The membrane-bound bacterial D-alanyl- D-alanine peptidases or penicillin-binding proteins (PBPs) catalyze the final transpeptidation reaction of bacterial cell wall biosynthesis and are the targets of beta-lactam antibiotics. Rather surprisingly, the substrate specificity of these enzymes is not well understood. In this paper, we present measurements of the reactivity of typical ... More
Mechanisms of action of corilagin and tellimagrandin I that remarkably potentiate the activity of beta-lactams against methicillin-resistant Staphylococcus aureus.
AuthorsShiota S, Shimizu M, Sugiyama J, Morita Y, Mizushima T, Tsuchiya T
JournalMicrobiol Immunol
PubMed ID14734860
'Corilagin and tellimagrandin I are polyphenols isolated from the extract of Arctostaphylos uvaursi and Rosa canina L. (rose red), respectively. We have reported that corilagin and tellimagrandin I remarkably reduced the minimum inhibitory concentration (MIC) of beta-lactams in methicillin-resistant Staphylococcus aureus(MRSA). In this study, we investigated the effect of corilagin ... More
Role of the rapA gene in controlling antibiotic resistance of Escherichia coli biofilms.
AuthorsLynch SV, Dixon L, Benoit MR, Brodie EL, Keyhan M, Hu P, Ackerley DF, Andersen GL, Matin A,
JournalAntimicrob Agents Chemother
PubMed ID17664315
'By using a high-throughput screening method, a mutant of a uropathogenic Escherichia coli strain affected in the rapA gene was isolated. The mutant formed normal-architecture biofilms but showed decreased penicillin G resistance, although the mutation did not affect planktonic cell resistance. Transcriptome analysis showed that 22 genes were down-regulated in ... More
Probing the catalytic activity of a cell division-specific transpeptidase in vivo with beta-lactams.
AuthorsEberhardt C, Kuerschner L, Weiss DS
JournalJ Bacteriol
PubMed ID12813065
'Penicillin-binding protein 3 (PBP3; also called FtsI) is a transpeptidase that catalyzes cross-linking of the peptidoglycan cell wall in the division septum of Escherichia coli. To determine whether the catalytic activity of PBP3 is activated during division, we assayed acylation of PBP3 with three beta-lactams (cephalexin, aztreonam, and piperacillin) in ... More
Diversity of penicillin-binding proteins. Resistance factor FmtA of Staphylococcus aureus.
AuthorsFan X, Liu Y, Smith D, Konermann L, Siu KW, Golemi-Kotra D,
JournalJ Biol Chem
PubMed ID17925392
'Antibiotic-resistant Staphylococcus aureus is a major concern to public health. Methicillin-resistant S. aureus strains are completely resistant to all beta-lactams antibiotics. One of the main factors involved in methicillin resistance in S. aureus is the penicillin-binding protein, PBP2a. This protein is insensitive to inactivation by beta-lactam antibiotics such as methicillin. ... More
Inhibition of Bacterial DD-Peptidases (Penicillin-Binding Proteins) in Membranes and in Vivo by Peptidoglycan-Mimetic Boronic Acids.
AuthorsDzhekieva L, Kumar I, Pratt RF,
JournalBiochemistry
PubMed ID22443299
'The DD-peptidases or penicillin-binding proteins (PBPs) catalyze the final steps of bacterial peptidoglycan biosynthesis and are inhibited by the ß-lactam antibiotics. There is at present a question of whether the active site structure and activity of these enzymes is the same in the solubilized (truncated) DD-peptidase constructs employed in crystallographic ... More
Penicillin-binding proteins of Bacteroides fragilis and their role in the resistance to imipenem of clinical isolates.
AuthorsAyala J, Quesada A, Vadillo S, Criado J, Píriz S,
JournalJ Med Microbiol
PubMed ID16192437
'In this study penicillin-binding proteins (PBPs) of Bacteroides fragilis and the resistance mechanisms of this micro-organism to 11 beta-lactam antibiotics were analysed. The study focused on the role of PBP2Bfr and metallo-beta-lactamase in the mechanism of resistance to imipenem. The mechanism of beta-lactam resistance in B. fragilis was strain dependent. ... More
Novel mutations in a patient isolate of Streptococcus agalactiae with reduced penicillin susceptibility emerging after long-term oral suppressive therapy.
AuthorsLongtin J, Vermeiren C, Shahinas D, Tamber GS, McGeer A, Low DE, Katz K, Pillai DR,
JournalAntimicrob Agents Chemother
PubMed ID21383092
'Penicillin nonsusceptibility has been demonstrated in group B streptococci (GBS), but there is limited information regarding mechanisms of resistance. We report a case of GBS with reduced susceptibility to penicillin emerging after long-term suppressive oral penicillin therapy for a prosthetic joint infection. Molecular characterization of the isolate before and after ... More
Fluorescent Bocillins: synthesis and application in the detection of penicillin-binding proteins.
AuthorsGee KR, Kang HC, Meier TI, Zhao G, Blaszcak LC
JournalElectrophoresis
PubMed ID11332764
Novel fluorescent analogs of penicillin V were synthesized and evaluated for efficacy in the detection of penicillin binding proteins (PBPs). These molecules include the full structure of penicillin V, with the potent Bodipy fluorophore attached to the para-position of the penicillin V phenyl group. The green fluorescent Bocillin FL and ... More
Flow cytometry as a rapid test for detection of penicillin resistance directly in bacterial cells in Enterococcus faecalis and Staphylococcus aureus.
AuthorsJarzembowski T, Wisniewska K, Józwik A, Bryl E, Witkowski J,
JournalCurr Microbiol
PubMed ID18574630
We studied the usefulness of flow cytometry for detection of penicillin resistance in E. faecalis and S. aureus by direct binding of commercially available fluorescent penicillin, Bocillin FL, to cells obtained from culture. There were significantly lower percentages of fluorescent cells and median and mean fluorescence values per particle in ... More
Rainbow's end: the quest for multiplexed fluorescence quantitative analysis in proteomics.
AuthorsPatton WF, Beechem JM
JournalCurr Opin Chem Biol
PubMed ID11827825
During the past two years, the performance of fluorescence-based protein detection methods has demonstrably eclipsed conventional technologies such as colloidal Coomassie Blue and silver staining with respect to detection sensitivity, quantitative accuracy and compatibility with modern protein identification and characterization procedures. At this point, fluorescence-based methods are poised to offer ... More
Specialized peptidoglycan hydrolases sculpt the intra-bacterial niche of predatory Bdellovibrio and increase population fitness.
Bdellovibrio are predatory bacteria that have evolved to invade virtually all gram-negative bacteria, including many prominent pathogens. Upon invasion, prey bacteria become rounded up into an osmotically stable niche for the Bdellovibrio, preventing further superinfection and allowing Bdellovibrio to replicate inside without competition, killing the prey bacterium and degrading its ... More
AmpH, a bifunctional DD-endopeptidase and DD-carboxypeptidase of Escherichia coli.
AuthorsGonzález-Leiza SM, de Pedro MA, Ayala JA,
JournalJ Bacteriol
PubMed ID22001512
In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display DD-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC ß-lactamases. AmpH has been ... More
Chemical-biological studies of subcellular organization in bacteria.
AuthorsFoss MH, Eun YJ, Weibel DB,
JournalBiochemistry
PubMed ID21823588
The subcellular organization of biological molecules is a critical determinant of many bacterial processes, including growth, replication of the genome, and division, yet the details of many mechanisms that control intracellular organization remain unknown. Decoding this information will impact the field of bacterial physiology and can provide insight into eukaryotic ... More
PBP5, PBP6 and DacD play different roles in intrinsic ß-lactam resistance of Escherichia coli.
AuthorsSarkar SK, Dutta M, Chowdhury C, Kumar A, Ghosh AS,
JournalMicrobiology
PubMed ID21719544
Escherichia coli PBP5, PBP6 and DacD, encoded by dacA, dacC and dacD, respectively, share substantial amino acid identity and together constitute ~50?% of the total penicillin-binding proteins of E. coli. PBP5 helps maintain intrinsic ß-lactam resistance within the cell. To test if PBP6 and DacD play simlar roles, we deleted ... More
Analysis of penicillin-binding proteins (PBPs) in carbapenem resistant Acinetobacter baumannii.
AuthorsVashist J, Tiwari V, Das R, Kapil A, Rajeswari MR,
JournalIndian J Med Res
PubMed ID21441690
Acinetobacter baumannii is a Gram-negative, cocco-bacillus aerobic pathogen responsible for nosocomial infections in hospitals. In the recent past A. baumannii had developed resistance against ß-lactams, even against carbapenems. Penicillin-binding proteins (PBPs) are crucial for the cell wall biosynthesis during cell proliferation and these are the target for ß-lactams. Therefore, the ... More
Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus.
The cell wall of Staphylococcus aureus is characterized by an extremely high degree of cross-linking within its peptidoglycan (PGN). Penicillin-binding protein 4 (PBP4) is required for the synthesis of this highly cross-linked peptidoglycan. We found that wall teichoic acids, glycopolymers attached to the peptidoglycan and important for virulence in Gram-positive ... More
Comparative study of the susceptibilities of major epidemic clones of methicillin-resistant Staphylococcus aureus to oxacillin and to the new broad-spectrum cephalosporin ceftobiprole.
AuthorsChung M, Antignac A, Kim C, Tomasz A,
JournalAntimicrob Agents Chemother
PubMed ID18505853
Multidrug-resistant strains of Staphylococcus aureus continue to increase in frequency worldwide, both in hospitals and in the community, raising serious problems for the chemotherapy of staphylococcal disease. Ceftobiprole (BPR; BAL9141), the active constituent of the prodrug ceftobiprole medocaril (BAL5788), is a new cephalosporin which was already shown to have powerful ... More
First molecular characterization of group B streptococci with reduced penicillin susceptibility.
AuthorsKimura K, Suzuki S, Wachino J, Kurokawa H, Yamane K, Shibata N, Nagano N, Kato H, Shibayama K, Arakawa Y,
JournalAntimicrob Agents Chemother
PubMed ID18490507
Group B streptococci (GBS; Streptococcus agalactiae) are the leading cause of neonatal invasive diseases and are also important pathogens for adults. Penicillins are the drugs of first choice for the treatment of GBS infections, since GBS have been regarded to be uniformly susceptible to penicillins so far. Here we characterize ... More
Highly variable penicillin resistance determinants PBP 2x, PBP 2b, and PBP 1a in isolates of two Streptococcus pneumoniae clonal groups, Poland 23F-16 and Poland 6B-20.
AuthorsIzdebski R, Rutschmann J, Fiett J, Sadowy E, Gniadkowski M, Hryniewicz W, Hakenbeck R,
JournalAntimicrob Agents Chemother
PubMed ID18160523
Penicillin-binding proteins (PBPs) in representatives of two Streptococcus pneumoniae clonal groups that are prevalent in Poland, Poland 23F-16 and Poland 6B-20, were investigated by PBP profile analysis, antibody reactivity pattern analysis, and DNA sequence analysis of the transpeptidase (TP) domain-encoding regions of the pbp2x, pbp2b, and pbp1a genes. The isolates ... More
Function of penicillin-binding protein 2 in viability and morphology of Pseudomonas aeruginosa.
To investigate the function of penicillin-binding protein 2 (PBP 2) in Pseudomonas aeruginosa PAO1. The growth and morphology of P. aeruginosa cultured in the absence and presence of mecillinam was assessed. The gene encoding PBP 2, pbpA, was identified in the genome of P. aeruginosa PAO1 and both its full-length ... More
Structure-activity relationships of different beta-lactam antibiotics against a soluble form of Enterococcus faecium PBP5, a type II bacterial transpeptidase.
AuthorsHujer AM, Kania M, Gerken T, Anderson VE, Buynak JD, Ge X, Caspers P, Page MG, Rice LB, Bonomo RA,
JournalAntimicrob Agents Chemother
PubMed ID15673741
Penicillin-binding proteins (PBPs) catalyze the essential reactions in the biosynthesis of cell wall peptidoglycan from glycopeptide precursors. beta-Lactam antibiotics normally interfere with this process by reacting covalently with the active site serine to form a stable acyl-enzyme. The design of novel beta-lactams active against penicillin-susceptible and penicillin-resistant organisms will require ... More
Restoration of susceptibility of methicillin-resistant Staphylococcus aureus to beta-lactam antibiotics by acidic pH: role of penicillin-binding protein PBP 2a.
Methicillin-resistant Staphylococcus aureus (MRSA) is a global scourge, and treatment options are becoming limited. The MRSA phenotype reverts to that of beta-lactam-sensitive S. aureus when bacteria are grown at pH 5.0 in broth and, more importantly from a medical perspective (protracted, relapsing infections), after phagocytosis by macrophages, where the bacteria ... More
BOCILLIN FL, a sensitive and commercially available reagent for detection of penicillin-binding proteins.
We describe a new, sensitive, rapid, and nonradioactive method involving the use of the commercially available BOCILLIN FL, a fluorescent penicillin, as a labeling reagent for the detection and study of penicillin-binding proteins (PBPs). This method allowed rapid detection of 30 ng of a purified PBP protein under UV light ... More
Genetic analysis of the cell division protein FtsI (PBP3): amino acid substitutions that impair septal localization of FtsI and recruitment of FtsN.
AuthorsWissel MC, Weiss DS
JournalJ Bacteriol
PubMed ID14702319
FtsI (also called PBP3) of Escherichia coli is a transpeptidase required for synthesis of peptidoglycan in the division septum and is one of several proteins that localize to the septal ring. FtsI comprises a small cytoplasmic domain, a transmembrane helix, a noncatalytic domain of unknown function, and a catalytic (transpeptidase) ... More
Genetic and molecular characterization of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin.
Previous studies with beta-lactamase-negative, ampicillin-resistant (BLNAR) Haemophilus influenzae from Japan, France, and North America indicate that mutations in ftsI encoding PBP3 confer ampicillin MICs of 1 to 4 micro g/ml. Several BLNAR strains with ampicillin MICs of 4 to 16 micro g/ml recently isolated from North America were studied. Pulsed-field ... More
The cell-shape protein MreC interacts with extracytoplasmic proteins including cell wall assembly complexes in Caulobacter crescentus.
AuthorsDivakaruni AV, Loo RR, Xie Y, Loo JA, Gober JW
JournalProc Natl Acad Sci U S A
PubMed ID16344480
The bacterial actin homolog, MreB, forms helical cables within the cell that are required for maintenance of a rod shape. These helical structures are thought to be involved in the spatial organization of cell wall (peptidoglycan) synthesizing complexes of penicillin-binding proteins (PBPs). Here, we examined the role of the MreC ... More
Structure of the Peptidoglycan Synthase Activator LpoP in Pseudomonas aeruginosa.
Authors
JournalStructure
PubMed ID32320673
RNA polymerase mutations cause cephalosporin resistance in clinical Neisseria gonorrhoeae isolates.
Authors
JournalElife
PubMed ID32011233
Substitutions in PBP2b from β-Lactam-resistant Streptococcus pneumoniae Have Different Effects on Enzymatic Activity and Drug Reactivity.
Authors
JournalJ Biol Chem
PubMed ID28062575
Antibiotic-Induced Cell Chaining Triggers Pneumococcal Competence by Reshaping Quorum Sensing to Autocrine-Like Signaling.
Authors
JournalCell Rep
PubMed ID30485808
A central role for PBP2 in the activation of peptidoglycan polymerization by the bacterial cell elongation machinery.