scholarly journals Staphylococcus aureus Putative Vaccines Based on the Virulence Factors: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Bahman Mirzaei ◽  
Ryhaneh Babaei ◽  
Habib Zeighami ◽  
Maryam Dadar ◽  
Ali Soltani
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Nosocomial Infections ◽  
Recent Progress ◽  
Vaccine Development ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Vaccine Candidates ◽  
Healthcare Settings ◽  
The 1960S

Since the 1960s, the frequency of methicillin-resistant Staphylococcus aureus as a recurrent cause of nosocomial infections has increased. Since multidrug-resistant Staphylococcus has overcome antimicrobial treatment, the development of putative vaccines based on virulence factors could be a great help in controlling the infections caused by bacteria and are actively being pursued in healthcare settings. This mini-review provides an overview of the recent progress in vaccine development, immunogenicity, and therapeutic features of some S. aureus macromolecules as putative vaccine candidates and their implications against human S. aureus-related infections. Based on the reviewed experiments, multivalent vaccines could prevent the promotion of the diseases caused by this bacterium and enhance the prevention chance of S. aureus infections.

scholarly journals Staphylococcus aureus—A Known Opponent against Host Defense Mechanisms and Vaccine Development—Do We Still Have a Chance to Win?

2022 ◽  
Vol 23 (2) ◽  
pp. 948
Author(s):  
Urszula Wójcik-Bojek ◽  
Barbara Różalska ◽  
Beata Sadowska
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Therapy ◽  
Virulence Factors ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Vaccine Development ◽  
Global Trends ◽  
Molecular Microbiology ◽  
Modern Technologies ◽  
New Vaccines

The main purpose of this review is to present justification for the urgent need to implement specific prophylaxis of invasive Staphylococcus aureus infections. We emphasize the difficulties in achieving this goal due to numerous S. aureus virulence factors important for the process of infection and the remarkable ability of these bacteria to avoid host defense mechanisms. We precede these considerations with a brief overview of the global necessitiy to intensify the use of vaccines against other pathogens as well, particularly in light of an impasse in antibiotic therapy. Finally, we point out global trends in research into modern technologies used in the field of molecular microbiology to develop new vaccines. We focus on the vaccines designed to fight the infections caused by S. aureus, which are often resistant to the majority of available therapeutic options.

scholarly journals Interactions between staphylococcal enterotoxins A and D and superantigen-like proteins 1 and 5 for predicting methicillin and multidrug resistance profiles among Staphylococcus aureus ocular isolates

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254519
Author(s):  
Min Lu ◽  
Jean-Marie Parel ◽  
Darlene Miller
Keyword(s):  
Machine Learning ◽  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Virulence Factors ◽  
Phenotypic Expression ◽  
Multidrug Resistant ◽  
Machine Learning Techniques ◽  
Strong Interactions ◽  
Antibiotics Resistance ◽  
Gene Profiles

Background Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) S. aureus strains are well recognized as posing substantial problems in treating ocular infections. S. aureus has a vast array of virulence factors, including superantigens and enterotoxins. Their interactions and ability to signal antibiotics resistance have not been explored. Objectives To predict the relationship between superantigens and methicillin and multidrug resistance among S. aureus ocular isolates. Methods We used a DNA microarray to characterize the enterotoxin and superantigen gene profiles of 98 S. aureus isolates collected from common ocular sources. The outcomes contained phenotypic and genotypic expressions of MRSA. We also included the MDR status as an outcome, categorized as resistance to three or more drugs, including oxacillin, penicillin, erythromycin, clindamycin, moxifloxacin, tetracycline, trimethoprim-sulfamethoxazole and gentamicin. We identified gene profiles that predicted each outcome through a classification analysis utilizing Random Forest machine learning techniques. Findings Our machine learning models predicted the outcomes accurately utilizing 67 enterotoxin and superantigen genes. Strong correlates predicting the genotypic expression of MRSA were enterotoxins A, D, J and R and superantigen-like proteins 1, 3, 7 and 10. Among these virulence factors, enterotoxin D and superantigen-like proteins 1, 5 and 10 were also significantly informative for predicting both MDR and MRSA in terms of phenotypic expression. Strong interactions were identified including enterotoxins A (entA) interacting with superantigen-like protein 1 (set6-var1_11), and enterotoxin D (entD) interacting with superantigen-like protein 5 (ssl05/set3_probe 1): MRSA and MDR S. aureus are associated with the presence of both entA and set6-var1_11, or both entD and ssl05/set3_probe 1, while the absence of these genes in pairs indicates non-multidrug-resistant and methicillin-susceptible S. aureus. Conclusions MRSA and MDR S. aureus show a different spectrum of ocular pathology than their non-resistant counterparts. When assessing the role of enterotoxins in predicting antibiotics resistance, it is critical to consider both main effects and interactions.

Anti-Virulence Strategy against the Multidrug-Resistant Bacterial Pathogen Pseudomonas aeruginosa: Pseudolysin (Elastase B) as a Potential Druggable Target

2019 ◽  
Vol 20 (5) ◽  
pp. 471-487 ◽  
Author(s):  
Anna Clara M. Galdino ◽  
Matheus P. de Oliveira ◽  
Teodorico C. Ramalho ◽  
Alexandre A. de Castro ◽  
Marta H. Branquinha ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Bacterial Pathogen ◽  
Intercellular Junctions ◽  
Multidrug Resistant ◽  
Complement Components ◽  
Healthcare Settings ◽  
Host Interaction ◽  
Promising Target ◽  
Hospital Acquired

Pseudomonas aeruginosa is a non-fermentative, gram-negative bacterium that is one of the most common pathogens responsible for hospital-acquired infections worldwide. The management of the infections caused by P. aeruginosa represents a huge challenge in the healthcare settings due to the increased emergence of resistant isolates, some of them resistant to all the currently available antimicrobials, which results in elevated morbimortality rates. Consequently, the development of new therapeutic strategies against multidrug-resistant P. aeruginosa is urgent and needful. P. aeruginosa is wellrecognized for its extreme genetic versatility and its ability to produce a lush variety of virulence factors. In this context, pseudolysin (or elastase B) outstands as a pivotal virulence attribute during the infectious process, playing multifunctional roles in different aspects of the pathogen-host interaction. This protein is a 33-kDa neutral zinc-dependent metallopeptidase that is the most abundant peptidase found in pseudomonal secretions, which contributes to the invasiveness of P. aeruginosa due to its ability to cleave several extracellular matrix proteins and to disrupt the basolateral intercellular junctions present in the host tissues. Moreover, pseudolysin makes P. aeruginosa able to overcome host defenses by the hydrolysis of many immunologically relevant molecules, including antibodies and complement components. The attenuation of this striking peptidase therefore emerges as an alternative and promising antivirulence strategy to combat antibiotic-refractory infections caused by P. aeruginosa. The anti-virulence approach aims to disarm the P. aeruginosa infective arsenal by inhibiting the expression/activity of bacterial virulence factors in order to reduce the invasiveness of P. aeruginosa, avoiding the emergence of resistance since the proliferation is not affected. This review summarizes the most relevant features of pseudolysin and highlights this enzyme as a promising target for the development of new anti-virulence compounds.

scholarly journals Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

2021 ◽  
Vol 12 ◽  
Author(s):  
Jonah Clegg ◽  
Elisabetta Soldaini ◽  
Rachel M. McLoughlin ◽  
Stephen Rittenhouse ◽  
Fabio Bagnoli ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Science Studies ◽  
Vaccine Development ◽  
Ex Vivo ◽  
Human Pathogens ◽  
Vaccine Candidates ◽  
Target Populations ◽  
Antibiotic Resistance Profile ◽  
Novel Therapeutic Strategies

Staphylococcus aureus is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to new antibiotics. Vaccine development efforts against S. aureus have failed so far however, the findings from these human clinical and non-clinical studies provide potential insight for such failures. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Translational science studies are attempting to discover correlates of protection using animal models as well as in vitro and ex vivo models assessing efficacy of vaccine candidates. Several new vaccine candidates are being tested in human clinical trials in a variety of target populations. In addition to vaccines, bacteriophages, monoclonal antibodies, centyrins and new classes of antibiotics are being developed. Some of these have been tested in humans with encouraging results. The complexity of the diseases and the range of the target populations affected by this pathogen will require a multipronged approach using different interventions, which will be discussed in this review.

Methicillin-Resistant Staphylococcus aureus and Other Multidrug-Resistant Colonizations/Infections in an Intensive Care Unit: Predictive Factors

2018 ◽  
Vol 21 (2) ◽  
pp. 190-197
Author(s):  
Elena Ochotorena ◽  
Juan José Hernández Morante ◽  
Rubén Cañavate ◽  
Roberto Andrés Villegas ◽  
Inmaculada Viedma
Keyword(s):  
Intensive Care Unit ◽  
Staphylococcus Aureus ◽  
Intensive Care ◽  
Hospital Stay ◽  
Nosocomial Infections ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Apache Ii Score ◽  
Methicillin Resistant ◽  
Mrsa Colonization

Introduction and Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is the most prevalent pathogen causing nosocomial infections in hospitals and health centers. This work is an effort to understand the epidemiology of MRSA and other multidrug-resistant pathogens in an intensive care unit (ICU) and to analyze characteristics that might determine the risk of MRSA colonization/infection in this unit. Method: An observational, 1-year prospective longitudinal study was conducted to obtain information about MRSA and other multidrug-resistant colonizations/infections. The study was conducted with ICU patients with an artificial airway. Data were obtained from the National Study of the Control of Nosocomial Infections in Intensive Care Units database. Results: MRSA colonization was highly prevalent (33%); however, other pathogens like gram(−) Bacillus showed a higher infectious potency. Acute Physiology and Chronic Health Evaluation (APACHE-II) score >15 and hospital stay of >4 days were the main variables that significantly predicted the risk of developing MRSA colonization ( p < .001 in both cases). Moreover, the presence of MRSA increased the risk of developing a second multidrug-resistant colonization/infection, especially with methicillin-resistant Pseudomona. Discussion: The high prevalence of MRSA emphasizes the need to continue studying risk factors for MRSA colonization/infection, which may allow early identification of this pathogen. Therefore, we propose the use of the APACHE-II score and length of hospital stay to predict increased risk of MRSA colonization. Awareness of the heightened risk in particular patients could lead to early detection and prevention.

scholarly journals Evolution and Epidemiology of Multidrug-Resistant Klebsiella pneumoniae in the United Kingdom and Ireland

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Danesh Moradigaravand ◽  
Veronique Martin ◽  
Sharon J. Peacock ◽  
Julian Parkhill
Keyword(s):  
United Kingdom ◽  
Klebsiella Pneumoniae ◽  
Large Scale ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Whole Genome ◽  
The Past ◽  
Healthcare Settings ◽  
The United Kingdom ◽  
Antimicrobial Resistance Genes

ABSTRACT Klebsiella pneumoniae is a human commensal and opportunistic pathogen that has become a leading causative agent of hospital-based infections over the past few decades. The emergence and global expansion of hypervirulent and multidrug-resistant (MDR) clones of K. pneumoniae have been increasingly reported in community-acquired and nosocomial infections. Despite this, the population genomics and epidemiology of MDR K. pneumoniae at the national level are still poorly understood. To obtain insights into these, we analyzed a systematic large-scale collection of invasive MDR K. pneumoniae isolates from hospitals across the United Kingdom and Ireland. Using whole-genome phylogenetic analysis, we placed these in the context of previously sequenced K. pneumoniae populations from geographically diverse countries and identified their virulence and drug resistance determinants. Our results demonstrate that United Kingdom and Ireland MDR isolates are a highly diverse population drawn from across the global phylogenetic tree of K. pneumoniae and represent multiple recent international introductions that are mainly from Europe but in some cases from more distant countries. In addition, we identified novel genetic determinants underlying resistance to beta-lactams, gentamicin, ciprofloxacin, and tetracyclines, indicating that both increased virulence and resistance have emerged independently multiple times throughout the population. Our data show that MDR K. pneumoniae isolates in the United Kingdom and Ireland have multiple distinct origins and appear to be part of a globally circulating K. pneumoniae population. IMPORTANCE Klebsiella pneumoniae is a major human pathogen that has been implicated in infections in healthcare settings over the past few decades. Antimicrobial treatment of K. pneumoniae infections has become increasingly difficult as a consequence of the emergence and spread of strains that are resistant to multiple antimicrobials. To better understand the spread of resistant K. pneumoniae, we studied the genomes of a large-scale population of extensively antimicrobial-resistant K. pneumoniae in the United Kingdom and Ireland by utilizing the fine resolution that whole-genome sequencing of pathogen genomes provides. Our results indicate that the K. pneumoniae population is highly diverse and that, in some cases, resistant strains appear to have spread across the country over a few years. In addition, we found evidence that some strains have acquired antimicrobial resistance genes independently, presumably in response to antimicrobial treatment. IMPORTANCE Klebsiella pneumoniae is a major human pathogen that has been implicated in infections in healthcare settings over the past few decades. Antimicrobial treatment of K. pneumoniae infections has become increasingly difficult as a consequence of the emergence and spread of strains that are resistant to multiple antimicrobials. To better understand the spread of resistant K. pneumoniae, we studied the genomes of a large-scale population of extensively antimicrobial-resistant K. pneumoniae in the United Kingdom and Ireland by utilizing the fine resolution that whole-genome sequencing of pathogen genomes provides. Our results indicate that the K. pneumoniae population is highly diverse and that, in some cases, resistant strains appear to have spread across the country over a few years. In addition, we found evidence that some strains have acquired antimicrobial resistance genes independently, presumably in response to antimicrobial treatment.

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

Open Medicine ◽  
2010 ◽  
Vol 5 (1) ◽  
pp. 12-29 ◽  
Author(s):  
Sanjai Saxena ◽  
Charu Gomber
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
High Throughput Screening ◽  
Vaccine Development ◽  
Multidrug Resistant ◽  
International Travel ◽  
Combinatorial Biosynthesis ◽  
Therapeutic Modalities ◽  
Staphylococcal Infections ◽  
New Chemical Entities

AbstractStaphylococcus aureus is the third most dreaded pathogen posing a severe threat due to its refractory behavior against the current armamentarium of antimicrobial drugs. This is attributed to the evolution of an array of resistance mechanisms responsible for morbidity and mortality globally. Local and international travel has resulted in the movement of drug resistant S. aureus clones from hospitals into communities and further into different geographical areas where they have been responsible for epidemic outbreaks. Thus, there is a dire necessity to refrain further cross movement of these multidrug resistant clones across the globe. The plausible alternative to prevent this situation is by thorough implementation of regulatory aspects of sanitation, formulary usage and development of new therapeutic interventions. Various strategies like exploring novel antibacterial targets, high throughput screening of microbes, combinatorial and synthetic chemistry, combinatorial biosynthesis and vaccine development are being extensively sought to overcome multidrug resistant chronic Staphylococcal infections. The majority of the antibacterial drugs are of microbial origin and are prone to being resisted. Anti-staphylococcal plant natural products that may provide a new alternative to overcome the refractory S.aureus under clinical settings have grossly been unnoticed. The present communication highlights the new chemical entities and therapeutic modalities that are entering the pharmaceutical market or are in the late stages of clinical evaluation to overcome multidrug resistant Staphylococcal infections. The review also explores the possibility of immunity and enzyme-based interventions as new therapeutic modalities and highlights the regulatory concerns on the prescription, usage and formulary development in the developed and developing world to keep the new chemical entities and therapeutic modalities viable to overcome antimicrobial resistance in S. aureus.

scholarly journals Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB)

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 339 ◽  
Author(s):  
Shweta Kailasan ◽  
Thomas Kort ◽  
Ipsita Mukherjee ◽  
Grant C. Liao ◽  
Tulasikumari Kanipakala ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rational Design ◽  
Vaccine Development ◽  
Polyclonal Antibodies ◽  
Neutralizing Antibody ◽  
Mortality And Morbidity ◽  
Vaccine Candidates ◽  
Novel Approach ◽  
Antibody Titers ◽  
Opsonophagocytic Killing

Staphylococcus aureus (SA) infections cause high mortality and morbidity in humans. Being central to its pathogenesis, S. aureus thwarts the host defense by secreting a myriad of virulence factors, including bicomponent, pore-forming leukotoxins. While all vaccine development efforts that aimed at achieving opsonophagocytic killing have failed, targeting virulence by toxoid vaccines represents a novel approach to preventing mortality and morbidity that are caused by SA. The recently discovered leukotoxin LukAB kills human phagocytes and monocytes and it is present in all known S. aureus clinical isolates. While using a structure-guided approach, we generated a library of mutations that targeted functional domains within the LukAB heterodimer to identify attenuated toxoids as potential vaccine candidates. The mutants were evaluated based on expression, solubility, yield, biophysical properties, cytotoxicity, and immunogenicity, and several fully attenuated LukAB toxoids that were capable of eliciting high neutralizing antibody titers were identified. Rabbit polyclonal antibodies against the lead toxoid candidate provided potent neutralization of LukAB. While the neutralization of LukAB alone was not sufficient to fully suppress leukotoxicity in supernatants of S. aureus USA300 isolates, a combination of antibodies against LukAB, α-toxin, and Panton-Valentine leukocidin completely neutralized the cytotoxicity of these strains. These data strongly support the inclusion of LukAB toxoids in a multivalent toxoid vaccine for the prevention of S. aureus disease.

scholarly journals Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris

mSystems ◽  
2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Daniel Zamith-Miranda ◽  
Heino M. Heyman ◽  
Sneha P. Couvillion ◽  
Radames J. B. Cordero ◽  
Marcio L. Rodrigues ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Nosocomial Infections ◽  
Pathogenic Fungus ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type

Candida auris is a recently described multidrug-resistant pathogenic fungus that is responsible for outbreaks across the globe, particularly in the context of nosocomial infections. Its virulence factors and pathogenesis are poorly understood.

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