Rapidly disseminating blaOXA-232 carrying Klebsiella pneumoniae belonging to ST231 in India: multiple and varied mobile genetic elements

Abstract

Background Recently, in India, there has been a shift from NDM to OXA48-like carbapenemases. OXA-181 and OXA-232 are the frequently produced variants of OXA48-like carbapenemases. OXA48-like carbapenemases are also known to be carried on transposons such as Tn 1999 , Tn 1999.2 and it is also associated with IS1R carried on Tn 1999 . In India, there are no previous reports studying the association of mobile genetic elements (MGEs) with OXA48-like carbapenemases. The present study was aimed at determining the genetic backbone of OXA48-like carbapenemases to determine the role of MGEs in its transfer and to investigate the Inc plasmid type carrying bla OXA48-like . Results A total of 49 carbapenem resistant K. pneumoniae which included 25 isolates from South India and 24 isolates from North India, were included in the study. Whole genome sequencing using Ion Torrent PGM was performed to study the isolates. OXA-232 was present in 35 isolates (71%). In 19 isolates (39%), bla OXA48-like was associated with MGEs. Insertion sequences such as ISX4, IS1, IS3, IS Kpn 1, IS Kpn 26, IS Kpn 25, IS Spu 2, IS Kox 1, IS 4321R , IS Ec 36, and IS Pa 38; and transposons such as TnAs3 and Tn2, were present. Isolates from northern and southern India belonging to same sequence type (ST) had diverse genetic backbone for bla OXA48-like . ST14 isolates from north had IS5 and Tn3 families while from south they had IS1, IS5 and IS630 families. ST231 from north had IS5, IS6 and Tn3 families with bla OXA-232 while from south, IS1, IS3 and IS5 families were observed; with IS Kpn 26 being present among isolates from both the regions. bla OXA48-like was predominantly found on ColKP3 plasmid. ST231 was the predominant ST in 22 isolates (45%). Conclusion OXA-232 is the predominant variant of OXA48-like carbapenemase with ST231 being the commonest ST of OXA48-like carbapenemase producing K. pneumoniae in India. Diverse MGEs have been associated with both bla OXA-232 and bla OXA-181 which contribute to their spread. The MGEs in the present study are different from those reported earlier. There is no clonal expansion of bla OXA48-like producing K. pneumoniae since diverse STs were observed. Monitoring the genetic backbone of OXA48-like carbapenemas...

<p>The First Egyptian Report Showing the Co-Existence of <em>bla</em>_NDM-25, <em>bla</em>_OXA-23, <em>bla</em>_OXA-181, and <em>bla</em>_GES-1 Among Carbapenem-Resistant <em>K. pneumoniae</em> Clinical Isolates Genotyped by BOX-PCR</p>

“…Although several reports have been published by some Asian countries like India 45 including Pakistan, 46 Bangladesh, 47 and Sri Lanka 48 indicating the existence of bla OXA-181 in CRKP, there are no Egyptian reports indicating the detection of bla OXA-181 or the coexistence of bla OXA-181 and bla NDM in CRKP clinical isolates. Based on the above, the current study investigated the existence of bla OXA-181 in CRKP and addressed the first report for the coexistence of bla OXA-181 and bla NDM in CRKP clinical isolates recovered from Egyptian patients.…”

The Characterization of OXA-232 Carbapenemase-Producing ST437 Klebsiella pneumoniae in China

“…Previously reports showed that the dominant epidemic ST in bla OXA-232 K. pneumoniae belonged to ST14 (France [ 7 ], the United States [ 14 , 15 ], South Korea [ 11 ], and Middle East [ 16 ]), ST15 (China [ 2 , 3 ] and Czech Republic [ 17 ]), ST16 (USA [ 14 ], Italy [ 18 ], and UK [ 10 ]), ST147 (India [ 19 ], Tunisia [ 20 ], and UK [ 10 ]), ST231 (Switzerland [ 12 ], the UK [ 10 ], Poland [ 21 ], Singapore [ 22 ], and Brunei Darussalam [ 13 ]), and ST395 (India [ 19 ] and UK [ 10 ]). Moreover, ST11 (India [ 19 ]) and hypervirulent ST23 (India [ 23 ]) OXA-232-producing K. pneumoniae have also been sporadically identified. In this research, we identified an OXA-232-producing strain belonging to ST437.…”

Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives Evolution

“…We found that in Indian settings the possible exchange of hvKp and CRKp plasmids might have occurred between the hvKp clone ST23 and the CRKp clone ST231. Although the direct proof of exchange is absent, we speculate that ST231 K. pneumoniae is the most prevalent sequence type of CRKp in the same setting (Shankar et al, 2019). Given the high frequency and the number of MDR plasmids acquired, the MDR hvKp BA4656 and BA34918 can be considered as a "real superbug" and it might have serious implications to public health.…”

“…The acquisition of the bla OXA-232 -bearing ColKP3 plasmid by a single isolate of hvKp may mark a major evolutionary step toward further establishment of clonal complex 23 (CC23). Till now, the clonal dissemination of bla OXA-232 -bearing K. pneumoniae majorly occurred by means of the ST231 carrying ColKP3 plasmid in India (Shankar et al, 2019). The emergence of carbapenemase producing hvKp in India can be hypothesized to be due to acquiring the ColKP3 plasmid from ST231 CRKp, as this sequence type is widely circulating in the same environment (Shankar et al, 2019).…”

“…Till now, the clonal dissemination of bla OXA-232 -bearing K. pneumoniae majorly occurred by means of the ST231 carrying ColKP3 plasmid in India (Shankar et al, 2019). The emergence of carbapenemase producing hvKp in India can be hypothesized to be due to acquiring the ColKP3 plasmid from ST231 CRKp, as this sequence type is widely circulating in the same environment (Shankar et al, 2019). Thus, the emergence of bla OXA-232 producing hvKp is particularly concerning due to its combination of hypervirulence and carbapenem resistance.…”