Analysis of the Effects of Cigarette Smoke on Staphylococcal Virulence Phenotypes

被引:57
作者
McEachern, Elisa K. [2 ]
Hwang, John H. [1 ,2 ]
Sladewski, Katherine M. [1 ,2 ]
Nicatia, Shari [1 ,2 ,3 ]
Dewitz, Carola [1 ,2 ,4 ]
Mathew, Denzil P. [1 ]
Nizet, Victor [5 ,6 ]
Alexander, Laura E. Crotty [1 ,2 ]
机构
[1] Vet Affairs San Diego Healthcare Syst, Med Serv, San Diego, CA 92161 USA
[2] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA
[3] Univ Utrecht, Dept Pharmaceut Sci, Utrecht, Netherlands
[4] Univ Vet Med, Dept Physiol Chem, Hannover, Germany
[5] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA
[6] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA
关键词
METHICILLIN-RESISTANT; NICOTINE EXPOSURE; TOBACCO-SMOKE; AUREUS; SKIN; MRSA; COLONIZATION; BACTEREMIA; MORTALITY; ADHESION;
D O I
10.1128/IAI.00303-15
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cigarette smoking is the leading preventable cause of death, disease, and disability worldwide. It is well established that cigarette smoke provokes inflammatory activation and impairs antimicrobial functions of human immune cells. Here we explore whether cigarette smoke likewise affects the virulence properties of an important human pathogen, Staphylococcus aureus, and in particular methicillin-resistant S. aureus (MRSA), one of the leading causes of invasive bacterial infections. MRSA colonizes the nasopharynx and is thus exposed to inhalants, including cigarette smoke. MRSA exposed to cigarette smoke extract (CSE-MRSA) was more resistant to macrophage killing (4-fold higher survival; P < 0.0001). CSE-MRSA demonstrated reduced susceptibility to cell lysis (1.78-fold; P = 0.032) and antimicrobial peptide (AMP) (LL-37) killing (MIC, 8 mu M versus 4 mu M). CSE modified the surface charge of MRSA in a dose-dependent fashion, impairing the binding of particles with charge similar to that of AMPs by 90% (P < 0.0001). These changes persisted for 24 h postexposure, suggesting heritable modifications. CSE exposure increased hydrophobicity by 55% (P < 0.0001), which complemented findings of increased MRSA adherence and invasion of epithelial cells. CSE induced upregulation of mprF, consistent with increased MRSA AMP resistance. S. aureus without mprF had no change in surface charge upon exposure to CSE. In vivo, CSE-MRSA pneumonia induced higher mouse mortality (40% versus 10%) and increased bacterial burden at 8 and 20 h postinfection compared to control MRSA-infected mice (P < 0.01). We conclude that cigarette smoke-induced immune resistance phenotypes in MRSA may be an additional factor contributing to susceptibility to infectious disease in cigarette smokers.
引用
收藏
页码:2443 / 2452
页数:10
相关论文
共 56 条
[1]   Pili mediate specific adhesion of Streptococcus pyogenes to human tonsil and skin [J].
Abbot, Emily L. ;
Smith, Wendy D. ;
Siou, Gerard P. S. ;
Chiriboga, Carlos ;
Smith, Rebecca J. ;
Wilson, Janet A. ;
Hirst, Barry H. ;
Kehoe, Michael A. .
CELLULAR MICROBIOLOGY, 2007, 9 (07) :1822-1833
[2]  
[Anonymous], 2014, HLTH CONSEQUENCES SM
[3]  
[Anonymous], 2011, Report on the global tobacco epidemic
[4]   Cigarette smoking and infection [J].
Arcavi, L ;
Benowitz, NL .
ARCHIVES OF INTERNAL MEDICINE, 2004, 164 (20) :2206-2216
[5]   Mannheimia haemolytica and Its Leukotoxin Cause Macrophage Extracellular Trap Formation by Bovine Macrophages [J].
Aulik, Nicole A. ;
Hellenbrand, Katrina M. ;
Czuprynski, Charles J. .
INFECTION AND IMMUNITY, 2012, 80 (05) :1923-1933
[6]   Mitogen-activated protein kinase Hog1 is activated in response to curcumin exposure in the budding yeast Saccharomyces cerevisiae [J].
Azad, Gajendra Kumar ;
Singh, Vikash ;
Thakare, Mayur Jankiram ;
Baranwal, Shivani ;
Tomar, Raghuvir Singh .
BMC MICROBIOLOGY, 2014, 14
[7]   Extranasal Methicillin-Resistant Staphylococcus aureus Colonization at Admission to an Acute Care Veterans Affairs Hospital [J].
Baker, Stacey E. ;
Brecher, Stephen M. ;
Robillard, Ernest ;
Strymish, Judith ;
Lawler, Elizabeth ;
Gupta, Kalpana .
INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY, 2010, 31 (01) :42-46
[8]   Activity of the major staphylococcal autolysin Atl [J].
Biswas, Raja ;
Voggu, Lalitha ;
Simon, Uwe Karsten ;
Hentschel, Petra ;
Thumm, Guenther ;
Goetz, Friedrich .
FEMS MICROBIOLOGY LETTERS, 2006, 259 (02) :260-268
[9]   Contribution of the Staphylococcus aureus Atl AM and GL Murein Hydrolase Activities in Cell Division, Autolysis, and Biofilm Formation [J].
Bose, Jeffrey L. ;
Lehman, McKenzie K. ;
Fey, Paul D. ;
Bayles, Kenneth W. .
PLOS ONE, 2012, 7 (07)
[10]   NORMAL KERATINIZATION IN A SPONTANEOUSLY IMMORTALIZED ANEUPLOID HUMAN KERATINOCYTE CELL-LINE [J].
BOUKAMP, P ;
PETRUSSEVSKA, RT ;
BREITKREUTZ, D ;
HORNUNG, J ;
MARKHAM, A ;
FUSENIG, NE .
JOURNAL OF CELL BIOLOGY, 1988, 106 (03) :761-771