Transfer of Penicillin Resistance BetweenNeisseriaein Microcosm

Abstract

Horizontal gene transfer between commensal and pathogenic Neisseriae is the mechanism proposed to explain how pathogenic species acquire altered portions of the penA gene, which encodes penicillin binding protein 2. These changes resulted in a moderately penicillin-resistant phenotype in the meningococci, whose frequency of isolation in Spain increased at the end of the 1980s. Little has been published about the possibility of this gene transfer in nature or about its simulation in the laboratory. We designed a simple microcosm, formed by solid and liquid media, that partially mimics the upper human respiratory tract. In this microcosm, penicillin-resistant commensal strains and the fully susceptible meningococcus were co-cultivated. The efficiency of gene transfer between the strains depended on the phase of bacterial growth and the conditions of culture. Resistance of penicillin was acquired in different steps irrespective of the source of the DNA. The presence of DNase in the medium had no effect on gene transfer, but it was near zero when nicked DNA was used. Cellto-cell contact or membrane blebs could explain these results. The analysis of sequences of the transpeptidase domain of PBP2 from transformants, and from donor and recipient strains demonstrated that the emergence of moderately resistant transformants was due to genetic exchange between the co-cultivated strains. Finally, mechanisms other than penA modification could be invoked to explain decreased susceptibility. 99

Natural transformation and phase variation modulation in Neisseria meningitidis

“…It has long been believed that horizontal exchange of genetic material among Neisseria is responsible for the mosaic nature of both virulence factors and housekeeping genes such as penA (Spratt et al ., 1992; Bowler et al ., 1994), aroE and glnA (Zhou et al ., 1997). In support of this hypothesis, in vitro co‐cultivation studies have provided evidence that such genetic exchange is feasible in nature (Frosch and Meyer, 1992; Bowler et al ., 1994; Orus and Vinas, 2000). A basic requirement for this type of DNA transfer to occur in vivo is the co‐colonization of the nasopharynx with different neisserial strains, serogroups and commensals.…”

Plasmid Diversity in Neisseriae

“…Other members of this genus, such as N. lactamica, N. sicca, N. flavescens, and various others, do not cause disease but can colonize the human nasopharynx and have been involved in antibiotic resistance transfer to N. meningitidis (21,28). Linz and coworkers have established that commensal neisseriae and N. meningitidis frequently exchange chromosomal DNA (17), consistent with the notion of a shared neisserial global gene pool (18).…”

Serotype Distribution, Antibiotic Susceptibility, and Genetic Relatedness ofNeisseria meningitidisStrains Recently Isolated in Italy

“…Surprisingly, no C:2bP.1.5 strain isolated in the examined period was PenI, unlike isolates with the same phenotype detected in other European countries [23] or in previous years in Italy. Interestingly, it has long been suggested that the exogenous DNA in the penA gene is responsible for the decreased affinity of PBP2 and, consequently, for higher MICs of penicillin [24].…”