Neutrophils and Bacterial Immune Evasion Kobayashi, Scott D; Malachowa, Natalia; DeLeo, Frank R
Journal of innate immunity,
01/2018, Letnik:
10, Številka:
5-6
Journal Article
Recenzirano
Odprti dostop
Neutrophils are an important component of the innate immune system and provide a front line of defense against bacterial infection. Although most bacteria are killed readily by neutrophils, some ...bacterial pathogens have the capacity to circumvent destruction by these host leukocytes. The ability of bacterial pathogens to avoid killing by neutrophils often involves multiple attributes or characteristics, including the production of virulence molecules. These molecules are diverse in composition and function, and collectively have the potential to alter or inhibit neutrophil recruitment, phagocytosis, bactericidal activity, and/or apoptosis. Here, we review the ability of bacteria to target these processes.
Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Infections that are caused by antibiotic-resistant strains often occur in epidemic waves that are initiated by ...one or a few successful clones. Methicillin-resistant S. aureus (MRSA) features prominently in these epidemics. Historically associated with hospitals and other health care settings, MRSA has now emerged as a widespread cause of community infections. Community or community-associated MRSA (CA-MRSA) can spread rapidly among healthy individuals. Outbreaks of CA-MRSA infections have been reported worldwide, and CA-MRSA strains are now epidemic in the United States. Here, we review the molecular epidemiology of the epidemic waves of penicillin- and methicillin-resistant strains of S. aureus that have occurred since 1940, with a focus on the clinical and molecular epidemiology of CA-MRSA.
Summary Meticillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide, and causes substantial morbidity and mortality. Health-care-associated MRSA infections arise in ...individuals with predisposing risk factors, such as surgery or presence of an indwelling medical device. By contrast, many community-associated MRSA (CA-MRSA) infections arise in otherwise healthy individuals who do not have such risk factors. Additionally, CA-MRSA infections are epidemic in some countries. These features suggest that CA-MRSA strains are more virulent and transmissible than are traditional hospital-associated MRSA strains. The restricted treatment options for CA-MRSA infections compound the effect of enhanced virulence and transmission. Although progress has been made towards understanding emergence of CA-MRSA, virulence, and treatment of infections, our knowledge remains incomplete. Here we review the most up-to-date knowledge and provide a perspective for the future prophylaxis or new treatments for CA-MRSA infections.
Bacteria such as
Staphylococcus aureus
are successful as commensal organisms or pathogens in part because they adapt rapidly to selective pressures imparted by the human host. Mobile genetic elements ...(MGEs) play a central role in this adaptation process and are a means to transfer genetic information (DNA) among and within bacterial species. Importantly, MGEs encode putative virulence factors and molecules that confer resistance to antibiotics, including the gene that confers resistance to beta-lactam antibiotics in methicillin-resistant
S. aureus
(MRSA). Inasmuch as MRSA infections are a significant problem worldwide and continue to emerge in epidemic waves, there has been significant effort to improve diagnostic assays and to develop new antimicrobial agents for treatment of disease. Our understanding of
S. aureus
MGEs and the molecules they encode has played an important role toward these ends and has provided detailed insight into the evolution of antimicrobial resistance mechanisms and virulence.
Vancomycin Resistance in Staphylococcus aureus McGuinness, Will A; Malachowa, Natalia; DeLeo, Frank R
The Yale journal of biology & medicine,
06/2017, Letnik:
90, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The evolution of
during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of ...methicillin-resistant
(MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections.
strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant
(VISA) (MIC = 4-8 µg/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis.
isolates with complete resistance to vancomycin (MIC ≥ 16 µg/mL) are termed vancomycin-resistant
(VRSA)-they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by the
gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in
, with an emphasis on the molecular mechanisms underlying vancomycin resistance.
Staphylococcus aureus is the leading cause of bacterial infections in developed countries and produces a wide spectrum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. ...Although S. aureus infections were historically treatable with common antibiotics, emergence of drug-resistant organisms is now a major concern. Methicillin-resistant S. aureus (MRSA) was endemic in hospitals by the late 1960s, but it appeared rapidly and unexpectedly in communities in the 1990s and is now prevalent worldwide. This Review focuses on progress made toward understanding the success of community-associated MRSA as a human pathogen, with an emphasis on genome-wide approaches and virulence determinants.
Staphylococcus aureus causes many types of human infections and syndromes—most notably skin and soft tissue infections. Abscesses are a frequent manifestation of S. aureus skin and soft tissue ...infections and are formed, in part, to contain the nidus of infection. Polymorphonuclear leukocytes (neutrophils) are the primary cellular host defense against S. aureus infections and a major component of S. aureus abscesses. These host cells contain and produce many antimicrobial agents that are effective at killing bacteria, but can also cause non-specific damage to host tissues and contribute to the formation of abscesses. By comparison, S. aureus produces several molecules that also contribute to the formation of abscesses. Such molecules include those that recruit neutrophils, cause host cell lysis, and are involved in the formation of the fibrin capsule surrounding the abscess. Herein, we review our current knowledge of the mechanisms and processes underlying the formation of S. aureus abscesses, including the involvement of polymorphonuclear leukocytes, and provide a brief overview of therapeutic approaches.
Staphylococcus aureus
has been an important human pathogen throughout history and is currently a leading cause of bacterial infections worldwide.
S. aureus
has the unique ability to cause a continuum ...of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. Moreover, the emergence of highly virulent, drug-resistant strains such as methicillin-resistant
S. aureus
in both healthcare and community settings is a major therapeutic concern. Neutrophils are the most prominent cellular component of the innate immune system and provide an essential primary defense against bacterial pathogens such as
S. aureus
. Neutrophils are rapidly recruited to sites of infection where they bind and ingest invading
S. aureus
, and this process triggers potent oxidative and non-oxidative antimicrobial killing mechanisms that serve to limit pathogen survival and dissemination.
S. aureus
has evolved numerous mechanisms to evade host defense strategies employed by neutrophils, including the ability to modulate normal neutrophil turnover, a process critical to the resolution of acute inflammation. Here we provide an overview of the role of neutrophils in host defense against bacterial pathogens and discuss strategies employed by
S. aureus
to circumvent neutrophil function.
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are predominantly those affecting skin and soft tissues. Although progress has been made, our knowledge of the ...molecules that contribute to the pathogenesis of CA-MRSA skin infections is incomplete. We tested the hypothesis that alphahemolysin (Hla) contributes to the severity of USA300 skin infections in mice and determined whether vaccination against Hla reduces disease severity. Isogenic hla-negative (Δhla) strains caused skin lesions in a mouse infection model that were significantly smaller than those caused by wild-type USA300 and Newman strains. Moreover, infection due to wild-type strains produced dermonecrotic skin lesions, whereas there was little or no dermonecrosis in mice infected with Δhla strains. Passive immunization with Hla-specific antisera or active immunization with a nontoxigenic form of Hla significantly reduced the size of skin lesions caused by USA300 and prevented dermonecrosis.We conclude that Hla is a potential target for therapeutics or vaccines designed to moderate severe S. aureus skin infections.
is among the leading causes of bacterial infections worldwide. The high burden of
among human and animal hosts, which includes asymptomatic carriage and infection, is coupled with a notorious ability ...of the microbe to become resistant to antibiotics. Notably,
has the ability to produce molecules that promote evasion of host defense, including the ability to avoid killing by neutrophils.
Significant progress has been made to better understand
-host interactions. These discoveries include elucidation of the role played by numerous
virulence molecules during infection. Based on putative functions, a number of these virulence molecules, including
alpha-hemolysin and protein A, have been identified as therapeutic targets. Although it has not been possible to develop a vaccine that can prevent
infections, monoclonal antibodies specific for
virulence molecules have the potential to moderate the severity of disease.
Therapeutic options for treatment of methicillin-resistant
(MRSA) are limited, and the microbe typically develops resistance to new antibiotics. New prophylactics and/or therapeutics are needed.
Research that promotes an enhanced understanding of
-host interaction is an important step toward developing new therapeutic approaches directed to moderate disease severity and facilitate treatment of infection. This research effort includes studies that enhance our view of the interaction of
with human neutrophils.
. 34, 452-470.
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