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.
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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].
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