Staphylococcus aureus (S aureus) is a gram-positive coccus (0.6 µm in diameter). First S aureus infection was reported by Ogston in 1881.Citation1 About 20% of all human population is persistently colonize with this bacterium. It is an important human pathogen, which has ability to cause both community and hospital – acquired diseases. S aureus generally colonizes on skin scratch to cause soft tissue injury but when gain access to blood stream; it can lead to serious clinical conditions including bacteremia, sepsis and death. The ability to cause these infection is due to result of several virulence factor this pathogen has developed to evade the recognition from host innate immune system and able to hide within the host cell either in a vacuole or in the cytoplasm.Citation2 In recent years, there has been a rapid emergence of community-associated methicillin-resistant S aureus infection (CA-MRSA) in general population of otherwise healthy individuals.Citation3 The immune compromised people, elderly and young children are at higher risk of infection due to widespread dissemination of drug resistant S aureus making it a serious global threat. Situation is further complicated due to lack of effective staphylococcal vaccine development, leaving vancomycin as one of the remaining useful antibiotics. Investigation of methicillin-sensitive S aureus (MSSA) strain and its interaction with the host cell can shed some light on the immune evasion mechanism of this pathogen.
Host innate immune cell are vigilant at all times and mount an immune response soon after any pathogen is recognized by these cells. Neutrophil and macrophage play a major role in this process. Phagocytosis by neutrophil is very crucial to the host innate defense against invading bacterium, which leads to intracellular killing of bacteria via production of reactive oxygen species (ROS) and proteolytic enzymes forming neutrophil extracellular traps (NETs). Bacterial destruction by neutrophil is amplified by opsonization of bacteria with help of complement proteins. Complement is major innate immune defense system and functions primarily to recognize and destroy invading pathogens.Citation4,10,11 Macrophages are pro-inflammatory mediators of bacterial infection and are critical for amplifying immune cell recruitment/activation pathways. Resident macrophages reside in virtually all tissues and act as first line of defense against microbial invasion. Macrophages exhibit potent phagocytic and antimicrobial activity. This process consist of phagosome formation and maturation, mature phagosome fuses with lysosome to form phagolysosome and eventually help clear the pathogen.Citation5 Thus understanding the fundamental mechanism by which S aureus is able to suppress the host defense and lower down the effectiveness of antibiotics is very critical as we seek better treatment and prevention strategies against this pathogen.
In the current issue, Lacoma and colleaguesCitation6 report the interaction of S aureus (Newman, MSSA) using a mouse alveolar macrophage (MH-S) cell line. The question whether S aureus is able to interfere with the normal process of phagocytosis during phagosome formation and phagolysosome maturation is examined in detail. They used colocolization technique to track the progression of maturation process using specific markers for early and late stages of phagolysosome. Result from these markers suggested a favorable niche that offers protection from host immunological and antimicrobial activity because after phagocytosis, the phagolysosome fusion is paused/ayed. Thus, S aureus was able to survive and replicate within the macrophage. Previously it was reported that S aureus favors an acidic environment and this strategy help intracellular survival.Citation7 Authors also investigated the contribution of acidic environment on S aureus survival in this model using lysotracker and found that acidification do not play a role in this mechanism.
Different studies have demonstrated that S. aureus is able to persist within different type of host cells with ability to adopt in those situation and express different factors. Recent report from Tranchemontagne et alCitation7 show that S aureus survived inside macrophage by inhibiting normal phagolysosomal formation causing its intracellular survival. Another study from Kulkarni et alCitation8 show that in response to exposure of cigarette smoke extract, S aureus was able to supress host immune response and also modulate several virulence genes which help its evasion from bactericidal function of leukocytes. Hume et.alCitation9 observed a differential cytokine response in different stain of mice during S aureus topical infection model. The Macrophage inflammatory peptide (MIP-2) level was highly elevated in C57BL/6 mouse but BALB/c mice had muted cytokine response, which suggest that S aureus may have shut down the cytokine response during active infection process to avoid host defenses.
In conclusion, data obtained from these in vitro studies and from different strain of mouse model should be interpreted with caution for their relevance to clinical outcome.
Disclosure
No conflict of interest.
References
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- Kennedy A d, Otto M, Braughton K R, Whitney A R, Chen L, Mathema B, Mediavilla J R, Byrne K A, Parkins L D, Tenover F C et al. Epidemic community –associated methicillin-resistant Staphylococcus aureus: Recent clonal expansion and diversification. PNAS. 2008;105:1327–1332. doi:https://doi.org/10.1073/pnas.0710217105. PMID:18216255.
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- Lacoma A, Cano V, Moranta D, Regueiro V, Domínguez-Villanueva D, Laabei M, González-Nicolau M, Ausina V, Prat C, Bengoechea J A. Investigating intracellular persistence of Staphylococcus aureus within a murine alveolar macrophage cell line. https://doi.org/https://doi.org/10.1080/21505594.2017.1361089.
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