Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus aureus Bacteremia

PLOS ONE, Dec 2019

Objectives Mannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients. Methods We conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (≥7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people. Results Patients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P = 0.019 and P = 0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83–196.37; P = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19–29.57; P = 0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12–63.39; P = 0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03–4.26; P = 0.040). Conclusions This is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089139&type=printable

Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus aureus Bacteremia

et al. (2014) Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus aureus Bacteremia. PLoS ONE 9(3): e89139. doi:10.1371/journal.pone.0089139 Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus aureus Bacteremia Yong Pil Chong 0 Ki-Ho Park 0 Eun Sil Kim 0 Mi-Na Kim 0 Sung-Han Kim 0 Sang-Oh Lee 0 Sang-Ho Choi 0 Jin-Yong Jeong 0 Jun Hee Woo 0 Yang Soo Kim 0 Robert B. Sim, Oxford University, United Kingdom 0 1 Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 2 Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 3 Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Republic of Korea, 4 Center for Antimicrobial Resistance and Microbial Genetics, University of Ulsan College of Medicine, Seoul, Republic of Korea, 5 Asan Institute of Life Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul , Republic of Korea Objectives: Mannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients. Methods: We conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia ($7 days) and 46 patients with resolving bacteremia (,3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/ C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people. Results: Patients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P = 0.019 and P = 0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83-196.37; P = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19-29.57; P = 0.025), and low/ deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12-63.39; P = 0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03-4.26; P = 0.040). Conclusions: This is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB. - Staphylococcus aureus bacteremia is one of the most common serious bacterial infections with high morbidity and mortality. Frequently, S. aureus bacteremia persists despite several days of appropriate antibiotic therapy. Persistent bacteremia accounts for 638% of S. aureus bacteremia episodes and is associated with poor clinical outcomes [14]. Several clinical and microbiological characteristics such as retention of infected devices, endovascular infection, metastatic infection, methicillin resistance, vancomycin minimal inhibitory concentration (MIC) of 2 mg/L, agr dysfunction, and resistance to host defense cationic peptides have been suggested as risk factors for persistent bacteremia [17]. However, these clinical and microbiological factors were not consistent among studies and could explain only a part of persistent S. aureus bacteremia. Because S. aureus infection is a consequence of the dynamic interaction between bacteria and host defense, some factors related with host response to S. aureus may contribute to persistent bacteremia. For S. aureus to invade the host and establish infection, multiple steps such as inoculation and colonization of tissue surfaces, invasion, evasion of the host response, and metastatic spread are required. After the establishment of S. aureus infection, antibiotic therapy plays an important role in the eradication of infection. In some patients with S. aureus infection, bacteremia persists despite appropriate antibiotic therapy. Decreased or defective host response to S. aureus may lead to persistent bacteremia. However, no study has characterized the host response associated with persistent S. aureus bacteremia. In animal and in vitro studies, mannose-binding lectin (MBL) has been demonstrated to play an important role in the control of S. aureus infection [811]. Ther (...truncated)


This is a preview of a remote PDF: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089139&type=printable

Yong Pil Chong, Ki-Ho Park, Eun Sil Kim, Mi-Na Kim, Sung-Han Kim, Sang-Oh Lee, Sang-Ho Choi, Jin-Yong Jeong, Jun Hee Woo, Yang Soo Kim. Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus aureus Bacteremia, PLOS ONE, 2014, Volume 9, Issue 3, DOI: 10.1371/journal.pone.0089139