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BRIEF COMMUNICATION
Year : 2016  |  Volume : 34  |  Issue : 1  |  Page : 85-87
 

Resistance to amoxicillin-clavulanate and its relation to virulence-related factors in Yersinia enterocolitica biovar 1A


1 Department of Microbiology, University of Delhi, South Campus, New Delhi, India
2 Department of Biophysics, University of Delhi, South Campus, New Delhi, India

Date of Submission10-Feb-2015
Date of Acceptance21-Jul-2015
Date of Web Publication15-Jan-2016

Correspondence Address:
J S Virdi
Department of Microbiology, University of Delhi, South Campus, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.174125

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 ~ Abstract 

Recent studies have reported that the virulence factors (VFs) were detected more frequently in amoxicillin-clavulanate (AMC) susceptible clinical isolates of Escherichia coli. Here, we have evaluated the relationship between VFs and AMC-resistance phenotype in clinical isolates of Y. enterocolitica biovar 1A. The presence/absence of VFs was compared with their minimum inhibitory concentrations for AMC in strains of two serovars. We observed that the strains of the serovar O: 6, 30-6, 31 showed a similar relationship between the number of VFs and resistance to clavulanic acid as in E. coli but not of serovar O: 6, 30. Variations in the promoters/complete coding sequences (CCDSs) of β-lactamase gene (bla A) or the serological characteristics could not account for unusual susceptibility to AMC displayed by the strains of the serovar O: 6, 30. Therefore, we speculate that since the clinical strains of serovar O: 6, 30-6, 31 originated from the environment they were less exposed to antibiotics compared to clinical strains of serovar O: 6, 30. Thus, AMC susceptibility seems to be influenced by factors other than serotypes or promoters/CCDS of β-lactamase genes.


Keywords: Amoxicillin-clavulanate, clinical, serovars, virulence, Yersinia enterocolitica


How to cite this article:
Singhal N, Kumar M, Virdi J S. Resistance to amoxicillin-clavulanate and its relation to virulence-related factors in Yersinia enterocolitica biovar 1A. Indian J Med Microbiol 2016;34:85-7

How to cite this URL:
Singhal N, Kumar M, Virdi J S. Resistance to amoxicillin-clavulanate and its relation to virulence-related factors in Yersinia enterocolitica biovar 1A. Indian J Med Microbiol [serial online] 2016 [cited 2019 Nov 20];34:85-7. Available from: http://www.ijmm.org/text.asp?2016/34/1/85/174125



 ~ Introduction Top


 Yersinia More Details enterocolitica, an important enteric pathogen is represented by more than 50 serovars and 6 biovars viz. 1A, 1B, 2, 3, 4 and 5. Studies have shown that strains of Y. enterocolitica classified as biovar 1A represents more than one subspecies.[1] These are known to possess more than 17 distinct O-antigen types.[2] The strains of biovar 1A have generally been regarded as 'non-pathogenic' due to lack of known chromosomal determinants of virulence and the plasmid for Yersinia virulence plasmid. However, this has been challenged by many recent studies suggesting the potential pathogenicity of Y. enterocolitica biovar 1A.[3],[4],[5] Amoxicillin-clavulanate (AMC) is one of the most commonly prescribed antimicrobial against enteric infections. It has been devised to overcome β-lactamase mediated resistance in enteric bacteria and restore the efficacy of β-lactam antibiotics. Clavulanic acid acts as an inhibitor by forming stable intermediates with β-lactamases, 'tying up' the enzyme, while the partner-lactam inhibits the drug-target in the bacterial cell.

In earlier studies, we identified and reported virulence-related genes in Y. enterocolitica biovar 1A, some of which might be related to the pathogenicity of clinical biovar 1A strains. These included Yersinia stable toxin B and insecticidal toxins [6] hemophore A, genes related to hemin storage system, type I secretion system, and flagellar hook proteins.[7] We also reported the susceptibilities of Y. enterocolitica biovar 1A strains to amoxicillin and AMC.[8]

In a recent study, an inverse relationship was reported between virulence and resistance to AMC in clinical isolates of  Escherichia More Details coli. It was observed that virulence factors (VFs) were detected more commonly in AMC-susceptible isolates, implying that there was a relationship between virulence and β-lactamase inhibition in E. coli.[9] In the light of this study published recently, we analyzed data from our earlier studies to see if any relationship existed between VFs and AMC-resistance phenotype in clinical isolates of Y. enterocolitica biovar 1A.


 ~ Methods Top


The presence/absence of VFs in six clinical strains of Y. enterocolitica biovar 1A of two serotypes namely O: 6, 30 and O: 6, 30-6; 31 was compared with their minimum inhibitory concentrations (MICs) for AMC. These serotypes were selected as an earlier study showed that serovars O: 6, 30 and O: 6, 30-6, 31 of Y. enterocolitica biovar 1A were highly heterogeneous.[10] The details of the strains, their laboratory accession numbers, VFs and MICs for AMC are summarized in [Table 1].
Table 1: Details of AMC-susceptibility and presence of virulence--related factors in strains of  Yersinia enterocolitica More Details biovar 1A

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 ~ Results and Discussion Top


We observed that the strains of serovar O: 6, 30-6;31 showed a similar relationship between the number of VFs and resistance to clavulanic acid as observed by Oteo et al.[9] for clinical isolates of E. coli. Lesser the number of virulence-related genes in strains of serovar O: 6, 30-6, 31 higher was their resistance to the β-lactamase inhibitor, resulting in a higher MIC for the AMC. However, strains of serovar O: 6, 30 displayed a heterogeneous relationship between the number of VFs and resistance to clavulanic acid. One clinical strain of serovar O: 6, 30 despite having only two VFs displayed low inhibitor resistance and consequently a low MIC for AMC. However, the other two strains with more VFs, exhibited more inhibitor-resistance, resulting in a higher MIC for AMC.

In a previous study, we also analyzed the promoters and complete coding sequence (CCDS) of β-lactamase gene bla A of each of the strain reported here.[8] From this, we inferred that the promoters and CCDS of β-lactamase gene (bla A) of all the three strains of serovar O: 6, 30 were identical as were the bla A of serovar O: 6, 30-6, 31. Thus, neither the variations in the β-lactamase gene sequence (bla A) nor the serological characteristics account for the unusual susceptibility to AMC displayed by the strains of the serovar O: 6, 30. Interestingly, the strains of serovar O: 6, 30 are usually reported from clinical cases of yersiniosis.[6] Whereas the strains of serovar O: 6, 30-6, 31 have been reported less commonly from clinical samples.[10] It has also been suggested that clinical strains of bioserovar 1A/O: 6, 30-6, 31 originated from environmental strains by host adaptation and genetic changes.[10] It might be speculated that given their environmental origin, the clinical strains of serovar O: 6, 30-6, 31 were exposed less to antibiotics compared to clinical strains of serovar O: 6, 30. Thus, the relationship between resistance to AMC and virulence-related factors might be dependent on characteristics other than serotypes or variations in gene sequences of β-lactamases.

This is the first study where the relationship between VFs and resistance to AMC has been investigated in strains of Y. enterocolitica biovar 1A. Further studies using biovars/serovars not represented in the present work, however, are required to corroborate these findings.

Acknowledgements

Neelja Singhal is thankful to UGC - Dr. D.S. Kothari Postdoctoral Fellowship and Start Up Research Grant (Young Scientists, SB/YS/LS-156/2014) of Science and Engineering Research Board (DST). The project was supported by Indian Council of Medical Research grant (Grant no. AMR/17/2011-ECD-1), DU-DST-PURSE grant and the UGC - Special Assistance Programme (DRS-I) to the Department of Microbiology, University of Delhi South Campus.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Sihvonen LM, Jalkanen K, Huovinen E, Toivonen S, Corander J, Kuusi M, et al. Clinical isolates of Yersinia enterocolitica biotype 1A represent two phylogenetic lineages with differing pathogenicity-related properties. BMC Microbiol 2012;12:208.  Back to cited text no. 1
    
2.
Bhagat N, Virdi JS. The enigma of Yersinia enterocolitica biovar 1A. Crit Rev Microbiol 2011;37:25-39.  Back to cited text no. 2
    
3.
Singh I, Bhatnagar S, Virdi JS. Isolation and characterization of Yersinia enterocolitica from diarrheic human subjects and other sources. Curr Sci 2003;84:1353-5.  Back to cited text no. 3
    
4.
MacDonald E, Heier BT, Nygård K, Stalheim T, Cudjoe KS, Skjerdal T, et al. Yersinia enterocolitica outbreak associated with ready-to-eat salad mix, Norway, 2011. Emerg Infect Dis 2012;18:1496-9.  Back to cited text no. 4
    
5.
Fredriksson-Ahomaa M, Cernela N, Hächler H, Stephan R. Yersinia enterocolitica strains associated with human infections in Switzerland 2001-2010. Eur J Clin Microbiol Infect Dis 2012;31:1543-50.  Back to cited text no. 5
    
6.
Bhagat N, Virdi JS. Distribution of virulence-associated genes in Yersinia enterocolitica biovar 1A correlates with clonal groups and not the source of isolation. FEMS Microbiol Lett 2007;266:177-83.  Back to cited text no. 6
    
7.
Kumar P, Virdi JS. Identification and distribution of putative virulence genes in clinical strains of Yersinia enterocolitica biovar 1A by suppression subtractive hybridization. J Appl Microbiol 2012;113:1263-72.  Back to cited text no. 7
    
8.
Singhal N, Kumar M, Virdi JS. Molecular analysis of ß-lactamase genes to understand their differential expression in strains of Yersinia enterocolitica biotype 1A. Sci Rep 2014;4:5270.  Back to cited text no. 8
    
9.
Oteo J, González-López JJ, Ortega A, Quintero-Zárate JN, Bou G, Cercenado E, et al. Inhibitor-resistant TEM- and OXA-1-producing Escherichia coli isolates resistant to amoxicillin-clavulanate are more clonal and possess lower virulence gene content than susceptible clinical isolates. Antimicrob Agents Chemother 2014;58:3874-81.  Back to cited text no. 9
    
10.
Mallik S, Virdi JS. Genetic relationships between clinical and non-clinical strains of Yersinia enterocolitica biovar 1A as revealed by multilocus enzyme electrophoresis and multilocus restriction typing. BMC Microbiol 2010;10:158.  Back to cited text no. 10
    



 
 
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