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LETTER TO EDITOR  
Year : 2022  |  Volume : 14  |  Issue : 3  |  Page : 125-127
Invasive listeriosis: Molecular determinants of virulence and antimicrobial resistance


1 Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Neurosciences, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Medicine - V, Christian Medical College, Vellore, Tamil Nadu, India

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Date of Submission13-May-2022
Date of Decision27-May-2022
Date of Acceptance04-Jun-2022
Date of Web Publication26-Aug-2022
 

How to cite this article:
Kumar N, Miraclin AT, Gunasekaran K, Veeraraghavan B. Invasive listeriosis: Molecular determinants of virulence and antimicrobial resistance. J Global Infect Dis 2022;14:125-7

How to cite this URL:
Kumar N, Miraclin AT, Gunasekaran K, Veeraraghavan B. Invasive listeriosis: Molecular determinants of virulence and antimicrobial resistance. J Global Infect Dis [serial online] 2022 [cited 2022 Sep 30];14:125-7. Available from: https://www.jgid.org/text.asp?2022/14/3/125/354703


Sir,

Human listeriosis causes severe disease and, when invasive, leads to high fatality rates. Clinical spectrum is varied with septicemia being more common, followed by meningoencephalitis in immunocompromised individuals and elderly.[1],[2],[3] Listeria monocytogenes (Lm) has a higher misdiagnosis rate with fast progression and poor prognosis.[4],[5] Conventional culture method using blood or cerebrospinal fluid is time-consuming and has very low positive detection rate.[6] Despite adequate antibiotic treatment, the overall mortality is still high (25%–30%) and neurological sequelae are frequent. In this short report, we describe three clinical cases of Lm identified using conventional method; subsequently, the strains were characterized using next-generation sequencing. The clinical and microbiological characteristics of the isolates of the three patients are summarized in [Table 1]. All the three patients had risk factors such as type 2 diabetes mellitus, systemic hypertension, chronic kidney disease stage 5, lung fibrosis, and malignancy (germ cell tumor), which leads to impaired cell-mediated immunity, further predisposing to severe infection. ResFinder revealed only fosX gene in all three genomes. Accordingly, the study isolates were resistant to cephalosporins and susceptible to ampicillin, penicillin, and SXT (Trimethoprim/Sulphamethoxazole). Very few compounds have a bactericidal effect on Lm cells. Ampicillin or penicillin G was reported to be the best treatment options for listeriosis based on their bacteriostatic effect. The combination of AMP/PEN in combination with gentamicin will enhance the bactericidal effect of the therapy.[7]
Table 1: Clinical and microbiological characteristics of listeria isolates

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Intrinsic resistance to cephalosporins was reported to be mediated by oatA mutations and PBP3 mutations. In the study isolates, the site of insertions and non-sense mutation in oatA were in S96A, D440E, after 433 DK insertion, after 442 DSKE insertion, A443T, S445A, S449N, E450G, K452N, E453Q, K456V, S463T, I470M, D539E, A576S, and A607S. Regions of mutations in PBP3 were G66S, N98D, D171E, A223D, P236A, T580A, K584A, E608Q, and I650V [Figure 1]. OatA mutants were known to induce early secretion of proinflammatory cytokines and chemokines in vivo, which recites the importance of oatA in limiting innate immune responses, thereby promoting bacterial survival in the host.[8] This insertional inactivation of lmo0441 and lmo2229 (coding PBP3 and PBPA2, respectively) greatly reduces the intrinsic resistance of Lm to cephalosporins.[9] The patient B, who had a favorable outcome, was initiated on ampicillin with gentamicin following the culture reports, hence showed clinical recovery. The patient C was initiated on carbapenem, which did not modify the disease course and led to adverse outcomes. In this study, insertions and mutations reported in oatA and PBP3 gene were known to be the primary mechanism of resistance to higher generation cephalosporins. This study adds to the existing evidence on the resistance mechanisms of Lm and emphasises the importance of microbiological diagnosis, and also indicates the significance of considering the host predisposition before initiating empirical therapy with higher antibiotics such as cephalosporins or carbapenems.
Figure 1: Protein multialignment showing insertions and mutations in oatA gene

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Research quality and ethics statement

The authors followed applicable EQUATOR Network (https://www.equator-network.org/) guidelines, notably the CARE guideline, during the conduct of this report.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Barbuddhe SB, Malik SV, Kumar JA, Kalorey DR, Chakraborty T. Epidemiology and risk management of listeriosis in India. Int J Food Microbiol 2012;154:113-8.  Back to cited text no. 1
    
2.
Schlech WF 3rd, Lavigne PM, Bortolussi RA, Allen AC, Haldane EV, Wort AJ, et al. Epidemic listeriosis – Evidence for transmission by food. N Engl J Med 1983;308:203-6.  Back to cited text no. 2
    
3.
Hernández-Milián A, García Gasalla M, Díaz Antolín P, Payeras Cifré A. Listeria monocytogenes disease. Rev Clín Espanõ 2014;214:110.  Back to cited text no. 3
    
4.
Pan XB, Wang ZX, Ma MH, Wang HB, Gan GF, Fan HN. Clinical case report on treatment of Listeria monocytogenes meningoencephalitis: Intrathecal injection. Clin Case Rep 2018;6:1845-8.  Back to cited text no. 4
    
5.
Doganay M. Listeriosis: Clinical presentation. FEMS Immunol Med Microbiol 2003;35:173-5.  Back to cited text no. 5
    
6.
Zhang X, Wang R, Luo J, Xia D, Zhou C. Detection of meningoencephalitis caused by Listeria monocytogenes with ischemic stroke-like onset using metagenomics next-generation sequencing: A case report. Medicine (Baltimore) 2021;100:e26802.  Back to cited text no. 6
    
7.
Hof H. Listeriosis: Therapeutic options. FEMS Immunol Med Microbiol 2003;35:203-5.  Back to cited text no. 7
    
8.
Aubry C, Goulard C, Nahori MA, Cayet N, Decalf J, Sachse M, et al. OatA, a peptidoglycan O-acetyltransferase involved in Listeria monocytogenes immune escape, is critical for virulence. J Infect Dis 2011;204:731-40.  Back to cited text no. 8
    
9.
Guinane CM, Cotter PD, Ross RP, Hill C. Contribution of penicillin-binding protein homologs to antibiotic resistance, cell morphology, and virulence of Listeria monocytogenes EGDe. Antimicrob Agents Chemother 2006;50:2824-8.  Back to cited text no. 9
    

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Correspondence Address:
Dr. Balaji Veeraraghavan
Department of Clinical Microbiology, Christian Medical College, Vellore - 632 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jgid.jgid_94_22

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2008 Journal of Global Infectious Diseases | Published by Wolters Kluwer - Medknow
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