Genetic Diversity of Penicillin-Resistant Neisseria meningitidis

Abstract

The genetic relatedness of 42 penicillin-resistant Neisseria meningitidis isolates obtained during a 2-year period from a single hospital was studied by multilocus enzyme electrophoresis and by restriction fragment length polymorphism (RFLP) analysis of penicillin-binding protein (PBP) 2 genes. The PBP 2 genes of 7 susceptible strains gave identical RFLP profiles. Sixteen different PBP 2 RFLP profiles were found among the 42 resistant strains, but 4 were found in greater than 1 resistant isolate. Multilocus enzyme electrophoresis revealed a high level of genetic diversity. Four clusters of resistant strains could be distinguished at a genetic distance of 0.75. Resistant strains with the most common PBP 2 RFLP profile were restricted to one of these clusters and may be derived from a common ancestral strain. However, resistant strains with the 3 other common RFLP profiles were distributed in two or more of the clusters.

Prospects for Vaccine Prevention of Meningococcal Infection

“…A small percentage of isolates from the United States have intermediate susceptibility to penicillin (MIC of 0.1 to 1.0 g/ml) but the clinical significance of this is not clear (183,301). Penicillin resistance has been reported in Spain and is mediated by changes in penicillin binding proteins (20,52). Other appropriate antibiotics for the treatment of invasive meningococcal infection include ceftriaxone or cefotaxime, antibiotics that are frequently used for empirical therapy of bacterial meningitis.…”

Antibiotic resistance in microbes

“…For example, in penicillin-resistant Neisseria meningitis, the penA gene contains two segments which show 22% divergence from the penA allele found in penicillin-sensitive strains, but which are identical to the corresponding regions from the penA gene of N. fla6escens, a commensal species [23]. The fact that more than 30 different mosaic genes have been found in 78 isolates of penicillin-resistant N. meningitis exemplifies the extent to which this mechanism is common in naturally transformable species [24,25]. Resistance to sulfonamide drugs is due to either the development or the acquisition of an altered dihydropteroate synthase (DHPS) with a decreased affinity for the inhibitor.…”

Multilocus sequence typing for global surveillance of meningococcal disease

“…In an attempt to provide an alternative typing paradigm, many methods based on DNA technology have been proposed, including: ribotyping (Woods et al, 1992), random amplified polymorphic DNA (RAPD) (Woods et al, 1994;Bart et al, 1998;Schmink et al, 2001); fluorescent amplified-fragment length polymorphism (AFLP) (Goulding et al, 2000), restriction fragment length polymorphism (RFLP) (Campos et al, 1992), multiple-locus variable-number tandem repeat analysis (MLVA) (Schouls et al, 2006), and pulsed-field gel electrophoresis (PFGE). PFGE, in particular, has been widely employed in the surveillance of diseases caused by enteric bacteria in the PulseNet network (Swaminathan et al, 2001Ribot et al, 2006), however it is not reliable in its identification of hyperinvasive meningococci and comparison among laboratories is difficult.…”