Penicillinase-Producing Plasmid Types in Neisseria gonorrhoeae Clinical Isolates from Australia

Abstract

h Penicillinase-producing Neisseria gonorrhoeae (PPNG) carrying the bla TEM-135 gene is of particular concern, as it is considered a stepping stone toward resistance to extended-spectrum cephalosporins. Here, we sought to characterize plasmid types and the occurrence of the bla TEM-135 gene for N. gonorrhoeae clinical isolates from Australia. We found that bla TEM-135 was prevalent in Australian PPNG and was detected on all three major plasmid types. High-level resistance to penicillin in Neisseria gonorrhoeae is conferred by plasmid-mediated penicillinase production. To date, seven different penicillinase-harboring gonococcal plasmid types have been described and comprise three main plasmid types (Asian, African, and Rio/Toronto plasmids) and four less common variants (Nimes, New Zealand, Johannesburg, and Australian plasmids) (1-7). There are two different penicillinase genes that may be carried by these plasmids, including the classical bla TEM-1 gene and the more recently described gonococcal bla TEM-135 gene (8). The bla gene is of concern as it is considered to be an intermediate between a penicillinase and an extended-spectrum ␤-lactamase (9) and is therefore considered a potential future threat to the effectiveness of N. gonorrhoeae treatment. The bla TEM-135 gene was first described in an isolate from Thailand (8) and has since been reported in various countries, including Canada (10), China (11), Japan (12), and Switzerland (13). However, there are now more recent data showing that bla has been present in gonococci since at least 1984, suggesting that the gene is not, as originally thought, a recent evolutionary event driven by selective pressure through the use of extended-spectrum cephalosporins (14).Data on the rate at which penicillinase-producing N. gonorrhoeae (PPNG) isolates carry the bla TEM-135 gene are limited, ranging from 9.4% (9/96 PPNG isolates) in Thailand (9) and 20% (2/10 PPNG isolates) in Japan (12) to 58% (66/114 PPNG isolates) in China (11). These studies also highlighted that bla TEM-135 may occur in distinct genetic backgrounds and suggested that the gene has continued to be shared among gonococci via horizontal genetic exchange, having been found on the Asian and Rio/Toronto plasmid types and across various multilocus sequence types (MLST) and N. gonorrhoeae multiantigen sequence types (NG-MAST) (8,11,12,14).In this study, we sought to characterize plasmid types and the occurrence of the bla TEM-135 gene in N. gonorrhoeae clinical isolates from Australia. A total of 351 PPNG clinical isolates were included in this study (Table 1). These were all PPNG isolates identified as part of a broader investigation of N. gonorrhoeae isolates (n ϭ 2,455) that were collected from throughout Australia in the first half of the year 2012 (7, 15). The isolates were initially determined to be PPNG on the basis of acidometric and nitrocefin disc testing and subsequently by real-time PCR (7). The DNA used for the real-time PCR testing was stored at Ϫ80°C until further investigation. Here, the DNA ...

Molecular epidemiology of penicillinase-producing Neisseria gonorrhoeae isolates in France

“…This observation corroborates the diversity and emergence of new STs described in previous studies focusing on the epidemiology of PPNG isolates [9,11e15]. Moreover, the STs that we identified were mostly different from those described in Europe [14,15], South America [13], Asia [12], and Australia [9]. Here, we found that 29.5% (52/176) of isolates belonged to four major clusters related to either ST1479 and ST1582 (10.2% and 8.5%, respectively), or to ST8922 and ST1285 (5.6% and 5.1%, respectively) ( Fig.…”

“…In our study, we found 8% (14/176) of the PPNG isolates to be harbouring the M182T variant of TEM-135 (Table 1), whereas previous studies found higher frequencies of this variant: 10% in Thailand [11], approximately 27% in Argentina, Australia, and the UK, [9,13,14] and 58% in China [12]. In the studies carried out in Thailand and Argentina, TEM-135 was mainly harboured by a Toronto/Rio plasmid [11,13], whereas the studies conducted in Australia and UK found a higher prevalence of African and Asian plasmids [9,14]. Here, we found that the bla TEM-135 gene was embedded in both the Toronto/Rio (6/14, 42.9%) and Asian (8/14, 57.1%) plasmids.…”

“…Concerning the plasmids harbouring the bla TEM gene, African plasmid was the most common (89.2%), followed by Asian (7.4%) and Toronto/Rio (3.4%) plasmids (Table 1). Previous studies highlighted African plasmid as the most prevalent plasmid in PPNG isolates, with representation between 72.5% and 82.3% [9,13,14], but various abundances of Toronto/Rio plasmid have been described, with a prevalence of 10% in Thailand and UK [11,14], 13% in Australia [9], and 26.6% in Argentina [13]. This difference in Toronto/Rio plasmid prevalence is of particular interest in TEM-135 epidemiology because Toronto/Rio plasmid is quasi-systematically associated with bla TEM-135 [9,13e15].…”

“…Recent studies have demonstrated the emergence of TEM-135, a variant of TEM-1 harbouring the M182T stabilizing mutation, in Asia [10e12], Australia [9], Argentina [13], and the UK [14]. Interestingly, this variant has been described in WHO European, African, American, Southeast Asian, and Western Pacific regions in a large collection of isolates [15].…”

Identification of TEM-135 β-Lactamase in Neisseria gonorrhoeae Strains Carrying African and Toronto Plasmids in Argentina

“…To date, eight plasmid types have been described in N. gonorrhoeae and named after their epidemiological origin as African, Toronto/Rio, Asian, Nîmes, New Zealand, Johannesburg, and Australian plasmids (5-7). The PPNG isolates carrying a bla TEM-135 gene were found in Thailand, Japan, and China and recently reported in Australia and 15 other countries (8)(9)(10)(11)(12). TEM-135 differs from TEM-1 by a single nucleotide substitution at position 539, resulting in a single amino acid substitution, M182T.…”