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Virulence Dec 2021is one of the most frequent worldwide causes of morbidity and mortality due to an infectious agent. This pathogen can cause a wide variety of diseases, ranging from... (Review)
Review
is one of the most frequent worldwide causes of morbidity and mortality due to an infectious agent. This pathogen can cause a wide variety of diseases, ranging from moderately severe skin infections to fatal pneumonia and sepsis. Treatment of infections is complicated by antibiotic resistance and a working vaccine is not available. There has been ongoing and increasing interest in the extraordinarily high number of toxins and other virulence determinants that produces and how they impact disease. In this review, we will give an overview of how initiates and maintains infection and discuss the main determinants involved. A more in-depth understanding of the function and contribution of virulence determinants to infection will enable us to develop anti-virulence strategies to counteract the lack of an anti- vaccine and the ever-increasing shortage of working antibiotics against this important pathogen.
Topics: Animals; Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Mice; Quorum Sensing; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Virulence; Virulence Factors
PubMed: 33522395
DOI: 10.1080/21505594.2021.1878688 -
Toxins Sep 2021is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. has a high level of... (Review)
Review
is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. has a high level of antibiotic resistance and is a common cause of infections in hospitals and the community. The rising prevalence of community-acquired methicillin-resistant (CA-MRSA), combined with the important severity of infections in general, has resulted in the frequent use of anti-staphylococcal antibiotics, leading to increasing resistance rates. Antibiotic-resistant continues to be a major health concern, necessitating the development of novel therapeutic strategies. uses a wide range of virulence factors, such as toxins, to develop an infection in the host. Recently, anti-virulence treatments that directly or indirectly neutralize toxins have showed promise. In this review, we provide an update on toxin pathogenic characteristics, as well as anti-toxin therapeutical strategies.
Topics: Anti-Bacterial Agents; Staphylococcus aureus; Toxins, Biological; Virulence; Virulence Factors
PubMed: 34678970
DOI: 10.3390/toxins13100677 -
Current Opinion in Microbiology Feb 2020Staphylococcus aureus is an opportunistic pathogen that normally colonizes the human anterior nares. At the same time, this pathogen is one of the leading causes of... (Review)
Review
Staphylococcus aureus is an opportunistic pathogen that normally colonizes the human anterior nares. At the same time, this pathogen is one of the leading causes of life-threatening bloodstream infections, such as sepsis and endocarditis. In this review we will present the current understanding of the pathogenesis of these invasive infections, focusing on the mechanisms of S. aureus clearance from the bloodstream by the immune system, and how this pathogen hijacks the host defense and coagulation systems and further interacts with the blood vessel endothelium. Additionally, we will delve into the regulatory mechanisms S. aureus employs during an invasive infection. These new insights into host-pathogen interactions show promising avenues for the development of novel therapies for treating bloodstream infections.
Topics: Animals; Bacteremia; Host-Pathogen Interactions; Humans; Staphylococcal Infections; Staphylococcus aureus; Virulence
PubMed: 32172183
DOI: 10.1016/j.mib.2020.02.005 -
Frontiers in Cellular and Infection... 2014Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and represents a significant burden on the healthcare system. S. aureus attachment... (Review)
Review
Staphylococcus aureus is a major cause of nosocomial and community-acquired infections and represents a significant burden on the healthcare system. S. aureus attachment to medical implants and host tissue, and the establishment of a mature biofilm, play an important role in the persistence of chronic infections. The formation of a biofilm, and encasement of cells in a polymer-based matrix, decreases the susceptibility to antimicrobials and immune defenses, making these infections difficult to eradicate. During infection, dispersal of cells from the biofilm can result in spread to secondary sites and worsening of the infection. In this review, we discuss the current understanding of the pathways behind biofilm dispersal in S. aureus, with a focus on enzymatic and newly described broad-spectrum dispersal mechanisms. Additionally, we explore potential applications of dispersal in the treatment of biofilm-mediated infections.
Topics: Animals; Biofilms; Humans; Staphylococcal Infections; Staphylococcus aureus
PubMed: 25566513
DOI: 10.3389/fcimb.2014.00178 -
The Yale Journal of Biology and Medicine Jun 2017The evolution of during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance.... (Review)
Review
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.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Staphylococcus aureus; Vancomycin Resistance
PubMed: 28656013
DOI: No ID Found -
Toxins Apr 2021is an opportunistic and versatile pathogen that can cause several diseases, which range from acute and destructive, to chronic and difficult-to-treat infections [...].
is an opportunistic and versatile pathogen that can cause several diseases, which range from acute and destructive, to chronic and difficult-to-treat infections [...].
Topics: Animals; Anti-Bacterial Agents; Drug Resistance; Enterotoxins; Host-Pathogen Interactions; Humans; Staphylococcal Infections; Staphylococcus aureus; Virulence
PubMed: 33921743
DOI: 10.3390/toxins13040287 -
Toxins Jun 2018is a microorganism resident in the skin and nasal membranes with a dreadful pathogenic potential to cause a variety of community and hospital-acquired infections. The... (Review)
Review
is a microorganism resident in the skin and nasal membranes with a dreadful pathogenic potential to cause a variety of community and hospital-acquired infections. The frequency of these infections is increasing and their treatment is becoming more difficult. The ability of to form biofilms and the emergence of multidrug-resistant strains are the main reasons determining the challenge in dealing with these infections. infectious capacity and its success as a pathogen is related to the expression of virulence factors, among which the production of a wide variety of toxins is highlighted. For this reason, a better understanding of toxins is needed to enable the development of new strategies to reduce their production and consequently improve therapeutic approaches. This review focuses on understanding the toxin-based pathogenesis of and their role on infectious diseases.
Topics: Animals; Bacterial Toxins; Communicable Diseases; Humans; Staphylococcal Infections; Staphylococcus aureus
PubMed: 29921792
DOI: 10.3390/toxins10060252 -
Microbiology Spectrum Mar 2019is a formidable pathogen capable of causing infections in different sites of the body in a variety of vertebrate animals, including humans and livestock. A major... (Review)
Review
is a formidable pathogen capable of causing infections in different sites of the body in a variety of vertebrate animals, including humans and livestock. A major contribution to the success of as a pathogen is the plethora of virulence factors that manipulate the host's innate and adaptive immune responses. Many of these immune modulating virulence factors are secreted toxins, cofactors for activating host zymogens, and exoenzymes. Secreted toxins such as pore-forming toxins and superantigens are highly inflammatory and can cause leukocyte cell death by cytolysis and clonal deletion, respectively. Coagulases and staphylokinases are cofactors that hijack the host's coagulation system. Exoenzymes, including nucleases and proteases, cleave and inactivate various immune defense and surveillance molecules, such as complement factors, antimicrobial peptides, and surface receptors that are important for leukocyte chemotaxis. Additionally, some of these secreted toxins and exoenzymes can cause disruption of endothelial and epithelial barriers through cell lysis and cleavage of junction proteins. A unique feature when examining the repertoire of secreted virulence factors is the apparent functional redundancy exhibited by the majority of the toxins and exoenzymes. However, closer examination of each virulence factor revealed that each has unique properties that have important functional consequences. This chapter provides a brief overview of our current understanding of the major secreted virulence factors critical for pathogenesis.
Topics: Animals; Bacterial Toxins; Humans; Staphylococcal Infections; Staphylococcus aureus
PubMed: 30873936
DOI: 10.1128/microbiolspec.GPP3-0039-2018 -
Microbiology Spectrum Mar 2019is usually regarded as a bacterial pathogen due to its ability to cause multiple types of invasive infections. Nevertheless, colonizes about 30% of the human... (Review)
Review
is usually regarded as a bacterial pathogen due to its ability to cause multiple types of invasive infections. Nevertheless, colonizes about 30% of the human population asymptomatically in the nares, either transiently or persistently, and can therefore be regarded a human commensal as well, although carriage increases the risk of infection. Whereas many facets of the infection processes have been studied intensively, little is known about the commensal lifestyle of . Recent studies highlight the major role of the composition of the highly variable nasal microbiota in promoting or inhibiting colonization. Competition for limited nutrients, trace elements, and epithelial attachment sites, different susceptibilities to host defense molecules and the production of antimicrobial molecules by bacterial competitors may determine whether nasal bacteria outcompete each other. This chapter summarizes our knowledge about mechanisms that are used by for efficient nasal colonization and strategies used by other nasal bacteria to interfere with its colonization. An improved understanding of naturally evolved mechanisms might enable us to develop new strategies for pathogen eradication.
Topics: Bacteria; Bacterial Physiological Phenomena; Humans; Microbiota; Nasal Cavity; Staphylococcal Infections; Staphylococcus aureus
PubMed: 31004422
DOI: 10.1128/microbiolspec.GPP3-0029-2018 -
International Journal of Molecular... Jan 2022Recently, the drawbacks arising from the overuse of antibiotics have drawn growing public attention. Among them, drug-resistance (DR) and even multidrug-resistance (MDR)... (Review)
Review
Recently, the drawbacks arising from the overuse of antibiotics have drawn growing public attention. Among them, drug-resistance (DR) and even multidrug-resistance (MDR) pose significant challenges in clinical practice. As a representative of a DR or MDR pathogen, can cause diversity of infections related to different organs, and can survive or adapt to the diverse hostile environments by switching into other phenotypes, including biofilm and small colony variants (SCVs), with altered physiologic or metabolic characteristics. In this review, we briefly describe the development of the DR/MDR as well as the classical mechanisms (accumulation of the resistant genes). Moreover, we use multidimensional scaling analysis to evaluate the MDR relevant hotspots in the recent published reports. Furthermore, we mainly focus on the possible non-classical resistance mechanisms triggered by the two important alternative phenotypes of the , biofilm and SCVs, which are fundamentally caused by the different global regulation of the population, such as the main quorum-sensing (QS) and agr system and its coordinated regulated factors, such as the SarA family proteins and the alternative sigma factor σB (SigB). Both the biofilm and the SCVs are able to escape from the host immune response, and resist the therapeutic effects of antibiotics through the physical or the biological barriers, and become less sensitive to some antibiotics by the dormant state with the limited metabolisms.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35163165
DOI: 10.3390/ijms23031241