Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation

Bowler, Lucas D.; Zhang, Qianyun; Riou, J.Y.; Spratt, Brian G.

doi:10.1128/jb.176.2.333-337.1994

Cited by 180 publications

(106 citation statements)

References 16 publications

(25 reference statements)

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“…After their introduction into N. meningitidis, by horizontal acquisition or by mutations, both types of sulfonamide resistance genes have spread among meningococci of different serogroups and serotypes under selective pressure from the frequent use of sulfonamides. The intraspecies transfer of genetic material has earlier been shown to result in hybrid penicillinbinding proteins encoding low levels of penicillin resistance (3). In this case the origin of the foreign DNA was shown to be two Neisseria commensal species, N. flavescens and N. cinerea (3).…”

Section: Discussionmentioning

confidence: 97%

“…This points to the possibility of interspecies transfer and the exchange of DNA among related bacteria. In parallel, the penA gene, encoding the penicillin-binding protein 2, in meningococcal strains with increased levels of resistance to penicillin was found to have mosaic structures with regions identical to those of the corresponding parts of the penA gene in Neisseria flavescens and Neisseria cinerea (3).…”

Section: Site-directed Mutagenesis Of the Meningococcal Dhps Genementioning

confidence: 98%

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Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species

et al. 1995

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Sulfonamide resistance in Neisseria meningitidis is mediated by altered forms of the chromosomal gene for the drug target enzyme dihydropteroate synthase. Sulfonamides have been used for decades both for prophylaxis and the treatment of meningococcal disease, and resistance is common. Two types of resistance determinants have been identified, and regions important for drug insusceptibility to the corresponding enzyme have been defined by site-directed mutagenesis. Both types of resistance traits have spread among strains of N. meningitidis of different serogroups and serotypes, and the large differences at the nucleotide level in a comparison of the resistance genes with the dhps genes of susceptible meningococci indicate the origin of one or maybe both types in other Neisseria species. One sulfonamide-sensitive strain of N. meningitidis was found to have a mosaic dhps gene with a central part identical to the corresponding part of a gonococcal strain. This observation supports the idea of an interspecies transfer of genetic material in Neisseria species as a mechanism for the development of chromosomally mediated resistance.Sulfonamides have played a very important part in antibacterial chemotherapy for 6 decades. Their target is the enzyme dihydropteroate synthase (DHPS) (EC 2.5.1.15), which catalyzes the formation of dihydropteroic acid in bacterial and some eucaryotic cells, but it is not present in human cells. This difference is the basis for the selective action of sulfonamide drugs, which act as competitive inhibitors of DHPS, thereby blocking folate biosynthesis in the bacterial cell (5). Sulfonamides are structural analogs to the normal substrate p-aminobenzoic acid and can indeed function as alternative substrates to produce a sulfa-containing pteroate analog (16,22). Chromosomal mutations in the dhps gene resulting in low levels of sulfonamide resistance (Ͻ0.05 mM) can be isolated in the laboratory (13,19), and naturally occurring resistance to high concentrations of sulfonamides (Ͼ0.5 mM) has been observed in gram-negative, enteric bacteria. This resistance is plasmid-borne and due to the presence of alternative drugresistant variants of the enzyme (23). Two such plasmid-encoded enzymes have been detected, and the nucleotide sequences of the corresponding genes have been determined (15,21,24).In Neisseria meningitidis, traits mediating high resistance (Ն0.5 mM) to sulfonamides were found to be located chromosomally (10,14). Most of the sulfonamide-resistant clinical strains of N. meningitidis were found to contain a dhps gene that was about 10% different from the corresponding gene in sulfonamide-sensitive isolates. From this large difference it was concluded that the resistance had been introduced by recombination rather than by mutation. One characteristic of these chromosomal resistance genes is an insertion of 6 bp, creating two extra codons in the sequence. Two sulfonamide-resistant strains of N. meningitidis differed in their sequences from this often-found form of resistance by lacking the 6-...

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Section: Discussionmentioning

confidence: 97%

Section: Site-directed Mutagenesis Of the Meningococcal Dhps Genementioning

confidence: 98%

Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species

et al. 1995

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“…N. meningitidis is naturally competent for transformation, which enables the horizontal transfer of DNA between strains, resulting in mosaic structures at genetic loci and a highly diverse meningococcal population (13,14). The penA gene is altered as a result of DNA transfer between meningococcal strains or from commensal Neisseria species (15)(16)(17)(18). We previously developed a rapid approach to define meningococcal penA alleles based on restriction fragment length polymorphism (RFLP).…”

mentioning

confidence: 99%

Correlation between Alterations of the Penicillin-binding Protein 2 and Modifications of the Peptidoglycan Structure in Neisseria meningitidis with Reduced Susceptibility to Penicillin G

Antignac

Boneca

Rousselle

et al. 2003

Journal of Biological Chemistry

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Reduced susceptibility to penicillin G in Neisseria meningitidis is directly correlated with alterations in the penA gene, which encodes the penicillin-binding protein 2 (PBP2). Using purified PBP2s from different backgrounds, we confirmed that the reduced susceptibility to penicillin G is associated with a decreased affinity of altered PBP2s for penicillin G. Infrared spectroscopy analysis using isogenic penicillin-susceptible strains and strains with reduced susceptibility to penicillin G suggested that the meningococcal cell wall is also modified in a penA-dependent manner. Moreover, reverse-phase high pressure liquid chromatography and mass spectrometry analysis of these meningococcal strains confirmed the modifications of peptidoglycan components and showed an increase in the peaks corresponding to pentapeptide-containing muropeptides. These results suggest that the D,D-transpeptidase and/or D,D-carboxypeptidase activities of PBP2 are modified by the changes in penA gene.

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“…Molecular studies have shown that many chromosomal genes from bacteria have a mosaic pattern (2,5,15,19) presumably as a result of recombination with DNA from heterologous sources (10,30,31). The mechanisms causing these patterns are, however, seldom known.…”

mentioning

confidence: 99%

Natural Transformation of Acinetobacter sp. Strain BD413 with Cell Lysates of Acinetobacter sp., Pseudomonas fluorescens , and Burkholderia cepacia in Soil Microcosms

Nielsen

Smalla²,

Elsas

2000

Appl Environ Microbiol

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To elucidate the biological significance of dead bacterial cells in soil to the intra-and interspecies transfer of gene fragments by natural transformation, we have exposed the kanamycin-sensitive recipient Acinetobacter sp. strain BD413(pFG4) to lysates of the kanamycin-resistant donor bacteria Acinetobacter spp., Pseudomonas fluorescens, and Burkholderia cepacia. Detection of gene transfer was facilitated by the recombinational repair of a partially (317 bp) deleted kanamycin resistance gene in the recipient bacterium. The investigation revealed a significant potential of these DNA sources to transform Acinetobacter spp. residing both in sterile and in nonsterile silt loam soil. Heat-treated (80°C, 15 min) cell lysates were capable of transforming strain BD413 after 4 days of incubation in sterile soil and for up to 8 h in nonsterile soil. Transformation efficiencies obtained in vitro and in situ with the various lysates were similar to or exceeded those obtained with conventionally purified DNA. The presence of cell debris did not inhibit transformation in soil, and the debris may protect DNA from rapid biological inactivation. Natural transformation thus provides Acinetobacter spp. with an efficient mechanism to access genetic information from different bacterial species in soil. The relatively short-term biological activity (e.g., transforming activity) of chromosomal DNA in soil contrasts the earlier reported long-term physical stability of DNA, where fractions have been found to persist for several weeks in soil. Thus, there seems to be a clear difference between the physical and the functional significance of chromosomal DNA in soil.

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Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation

Cited by 180 publications

References 16 publications

Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species

Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species

Correlation between Alterations of the Penicillin-binding Protein 2 and Modifications of the Peptidoglycan Structure in Neisseria meningitidis with Reduced Susceptibility to Penicillin G

Natural Transformation of Acinetobacter sp. Strain BD413 with Cell Lysates of Acinetobacter sp., Pseudomonas fluorescens , and Burkholderia cepacia in Soil Microcosms

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