Identification of the<i>Streptococcus gordonii glmM</i>gene encoding phosphoglucosamine mutase and its role in bacterial cell morphology, biofilm formation, and sensitivity to antibiotics

Shimazu, Kisaki; Takahashi, Yukihiro; Uchikawa, Yoshimori; Shimazu, Yoshihito; Yajima, Ayako; Takashima, Eizo; Aoba, Takaaki; Kawai, Kiyoshi

doi:10.1111/j.1574-695x.2008.00410.x

Cited by 32 publications

(32 citation statements)

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“…In the case of PNGM, recent reports indicate a growing recognition of the importance of this enzyme in bacterial virulence and infectivity (10,13,30,35,37). Therefore, inhibitors selective for the bacterial PNGMs that do not cross-react with related eukaryotic proteins, such as PGM, may find clinical utility as antimicrobial agents.…”

Section: Resultsmentioning

confidence: 99%

“…In Gram-negative organisms, these enzymes appear to be essential for viability (5,17,23,31). In Gram-positive organisms, reports to date suggest that this enzyme is not required for viability, but gene deletion studies show reduced virulence, increased susceptibility to antibiotics, and decreased biofilm formation (10,13,30,35,37). The role of PNGM in the virulence of Bacillus anthracis infections has not been examined, but the peptidoglycan of this organism is known to stimulate the host inflammatory response (12).…”

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confidence: 99%

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Crystal Structure of Bacillus anthracis Phosphoglucosamine Mutase, an Enzyme in the Peptidoglycan Biosynthetic Pathway

2011

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Phosphoglucosamine mutase (PNGM) is an evolutionarily conserved bacterial enzyme that participates in the cytoplasmic steps of peptidoglycan biosynthesis. As peptidoglycan is essential for bacterial survival and is absent in humans, enzymes in this pathway have been the focus of intensive inhibitor design efforts. Many aspects of the structural biology of the peptidoglycan pathway have been elucidated, with the exception of the PNGM structure. We present here the crystal structure of PNGM from the human pathogen and bioterrorism agent Bacillus anthracis. The structure reveals key residues in the large active site cleft of the enzyme which likely have roles in catalysis and specificity. A large conformational change of the C-terminal domain of PNGM is observed when comparing two independent molecules in the crystal, shedding light on both the apo-and ligand-bound conformers of the enzyme. Crystal packing analyses and dynamic light scattering studies suggest that the enzyme is a dimer in solution. Multiple sequence alignments show that residues in the dimer interface are conserved, suggesting that many PNGM enzymes adopt this oligomeric state. This work lays the foundation for the development of inhibitors for PNGM enzymes from human pathogens.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Crystal Structure of Bacillus anthracis Phosphoglucosamine Mutase, an Enzyme in the Peptidoglycan Biosynthetic Pathway

2011

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“…GlmM can catalyze the conversion of glucosamine-6-phosphate to glucosamine-1-phosphate, which is an essential step in the formation of the cell wall precursor UDP-Nacetylglucosamine (25). In Streptococcus gordonii, mutations in GlmM appear to influence bacterial cell growth and morphology, biofilm formation, and sensitivity to penicillins (26). The function of GlmM in A. baumannii is currently not well-known.…”

Section: A Total Of 35 Representativementioning

confidence: 99%

Evolution of Carbapenem-Resistant Acinetobacter baumannii Revealed through Whole-Genome Sequencing and Comparative Genomic Analysis

Liu

Zhang

et al. 2015

Antimicrob Agents Chemother

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bAcinetobacter baumannii is a globally important nosocomial pathogen characterized by an evolving multidrug resistance. A total of 35 representative clinical A. baumannii strains isolated from 13 hospitals in nine cities in China from 1999 to 2011, including 32 carbapenem-resistant and 3 carbapenem-susceptible A. baumannii strains, were selected for whole-genome sequencing and comparative genomic analysis. Phylogenetic analysis revealed that the earliest strain, strain 1999BJAB11, and two strains isolated in Zhejiang Province in 2004 were the founder strains of carbapenem-resistant A. baumannii. Ten types of AbaR resistance islands were identified, and a previously unreported AbaR island, which comprised a two-component response regulator, resistance-related proteins, and RND efflux system proteins, was identified in two strains isolated in Zhejiang in 2004. Multiple transposons or insertion sequences (ISs) existed in each strain, and these gradually tended to diversify with evolution. Some of these IS elements or transposons were the first to be reported, and most of them were mainly found in strains from two provinces. Genome feature analysis illustrated diversified resistance genes, surface polysaccharides, and a restriction-modification system, even in strains that were phylogenetically and epidemiologically very closely related. IS-mediated deletions were identified in the type VI secretion system region, the csuE region, and core lipooligosaccharide (LOS) loci. Recombination occurred in the heme utilization region, and intrinsic resistance genes (bla ADC and bla OXA-51-like variants) and three novel bla OXA-51-like variants (bla OXA-424 , bla OXA-425 , and bla OXA-426 ) were identified. Our results could improve the understanding of the evolutionary processes that contribute to the emergence of carbapenem-resistant A. baumannii strains and help elucidate the molecular evolutionary mechanism in A. baumannii. Acinetobacter baumannii is an important opportunistic pathogen that has caused severe nosocomial infections worldwide (1). Multidrug-resistant A. baumannii strains resistant to carbapenems have been increasingly reported worldwide, which raises serious concerns about the limited antimicrobial treatment options available (2). Our previous study indicated that the percentage of imipenem-and meropenem-resistant A. baumannii strains in China increased from 4.5% in 2003 to 61.7% in 2010 and from 4.5% in 2003 to 62.8% in 2010, respectively. In 2012, according to the Chinese Meropenem Surveillance Study (CMSS), the rates of A. baumannii susceptibility to imipenem and meropenem were 37.8% and 36.0%, respectively (3).A. baumannii rapidly develops multidrug resistance due to the presence of mobile genetic elements (MGEs), such as insertion sequences (ISs), transposons, and resistance islands (4). Many recent studies have highlighted the diversity in the genomic location, architecture, and content of resistance islands, demonstrating the dynamic nature of A. baumannii antibiotic resistance mechanisms and the adapt...

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“…Although GlmM is not essential for the growth of S. gordonii, its mutation may result in impaired and/or unusual peptidoglycan synthesis, leading to increased sensitivity of the glmM mutant to cell wall inhibitors and to morphological changes. All of these phenotypic changes are restored by the complementation with plasmid-borne glmM [14]. We have also shown that the glmM mutation results in increased sensitivity to polymorphonuclear leukocyte (PMN)-dependent killing, even though no differences in attachment to human PMNs were observed between the glmM mutant and the wild type of S. gordonii.…”

Section: Introductionmentioning

confidence: 88%

“…We previously reported that the S. gordonii DL1 phosphoglucosamine mutase (GlmM; EC 5.4.2.10) is involved in bacterial cell growth, morphology, biofilm formation, and sensitivity to penicillins [14]. GlmM catalyzes the interconversion of glucosamine-6-phosphate to glucosamine-1-phosphate, an essential step in the biosynthetic pathway that leads to the formation of peptidoglycan precursor uridine 5 0 -diphospho-N-acetylglucosamine [15].…”

Section: Introductionmentioning

confidence: 99%

Contribution of phosphoglucosamine mutase to determination of bacterial cell morphology in Streptococcus gordonii

et al. 2011

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Phosphoglucosamine mutase (GlmM; EC 5.4.2.10) catalyzes the interconversion of glucosamine-6-phosphate to glucosamine-1-phosphate, an essential step in the biosynthetic pathway leading to the formation of the peptidoglycan precursor uridine 5'-diphospho-N-acetylglucosamine. We have recently identified the gene (glmM) encoding the enzyme of Streptococcus gordonii, an early colonizer on the human tooth and an important cause of infective endocarditis, and indicated that the glmM mutation in S. gordonii appears to influence bacterial cell growth, morphology, and sensitivity to penicillins. Moreover, the glmM mutation results in increased sensitivity to polymorphonuclear leukocyte (PMN)-dependent killing. In the present study, we observed similarities in the utilization of sugar between the wild-type strain and the glmM mutant of S. gordonii when cultivated with medium containing 0.2% glucose, fructose, lactose, or sucrose. Morphological analyses clearly indicated that the glmM mutation causes marked elongation of the streptococcal chains, enlargement of bacterial cells, increased distortion of the bacterial cell surface, and defects in cell separation. These results suggest that mutations in glmM appear to influence bacterial cell growth and morphology, independent of the carbon source.

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Identification of theStreptococcus gordonii glmMgene encoding phosphoglucosamine mutase and its role in bacterial cell morphology, biofilm formation, and sensitivity to antibiotics

Cited by 32 publications

References 74 publications

Crystal Structure of Bacillus anthracis Phosphoglucosamine Mutase, an Enzyme in the Peptidoglycan Biosynthetic Pathway

Crystal Structure of Bacillus anthracis Phosphoglucosamine Mutase, an Enzyme in the Peptidoglycan Biosynthetic Pathway

Evolution of Carbapenem-Resistant Acinetobacter baumannii Revealed through Whole-Genome Sequencing and Comparative Genomic Analysis

Contribution of phosphoglucosamine mutase to determination of bacterial cell morphology in Streptococcus gordonii

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