Innovative approaches to treat Staphylococcus aureus biofilm-related infections

2017 ◽  
Vol 61 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Katharina Richter ◽  
Freija Van den Driessche ◽  
Tom Coenye
Keyword(s):  
Staphylococcus Aureus ◽  
Extracellular Matrix ◽  
Antimicrobial Resistance ◽  
Iron Metabolism ◽  
Communication System ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Antibiofilm Activity ◽  
Human Pathogen ◽  
Bacterial Communication

Many bacterial infections in humans and animals are caused by bacteria residing in biofilms, complex communities of attached organisms embedded in an extracellular matrix. One of the key properties of microorganisms residing in a biofilm is decreased susceptibility towards antimicrobial agents. This decreased susceptibility, together with conventional mechanisms leading to antimicrobial resistance, makes biofilm-related infections increasingly difficult to treat and alternative antibiofilm strategies are urgently required. In this review, we present three such strategies to combat biofilm-related infections with the important human pathogen Staphylococcus aureus: (i) targeting the bacterial communication system with quorum sensing (QS) inhibitors, (ii) a ‘Trojan Horse’ strategy to disturb iron metabolism by using gallium-based therapeutics and (iii) the use of ‘non-antibiotics’ with antibiofilm activity identified through screening of repurposing libraries.

scholarly journals Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
James V. Rogers ◽  
Veronica L. Hall ◽  
Charles C. McOsker
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Defense Mechanism ◽  
Treatment Options ◽  
Bacterial Biofilms ◽  
Host Immune System ◽  
New Antibiotics ◽  
Financial Burdens ◽  
Global Threat

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.

Characterization of Toxin Genes and Antimicrobial Susceptibility of Staphylococcus aureus from Retail Raw Chicken Meat

2018 ◽  
Vol 81 (4) ◽  
pp. 528-533 ◽  
Author(s):  
SUIXIA LI ◽  
PANPAN WANG ◽  
JIALIN ZHAO ◽  
LUHONG ZHOU ◽  
PENGFEI ZHANG ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Health Hazard ◽  
Toxin Gene ◽  
Potential Health ◽  
Toxin Genes ◽  
Genes Encoding ◽  
Potential Health Hazard

ABSTRACTThe aim of this study was to investigate the toxin gene profile and antimicrobial resistance of Staphylococcus aureus isolates from raw chicken in the People's Republic of China. In total, 289 S. aureus isolates were characterized by antimicrobial susceptibility testing, and genes encoding enterotoxins, exfoliative toxins, Panton-Valentine leukocidin, and toxic shock syndrome toxin were revealed by PCR. Overall, 46.0% of the isolates were positive for one or more toxin genes. A high proportion of toxin genes were pvl (26.6%), followed by sej (12.5%), sea (9.0%), seh (8.3%), seb (6.9%), sec (6.9%), sed (4.8%), sei (3.1%), and see (2.4%). None of the isolates harbored seg, tsst-1, or exfoliative toxin genes. In total, 29 toxin gene profiles were obtained, and pvl (10.7%) was the most frequent genotype, followed by sea (5.9%), seb (4.8%), and sej (4.2%). Furthermore, 99.7% of the strains were resistant to at least one of the tested antimicrobial agents, and 87.2% of them displayed multidrug resistance. Resistance was most frequently observed to trimethoprim-sulfamethoxazole and erythromycin (86.2% for each), followed by tetracycline (69.9%), amoxicillin–clavulanic acid (45.0%), and ampicillin (42.6%). None of the strains were resistant to vancomycin. This study indicates that S. aureus isolates from raw chicken harbored multiple toxin genes and exhibited multiple antimicrobial resistance, which represents a potential health hazard for consumers.

scholarly journals Critically important antimicrobial preparations for veterinary medicine

2018 ◽  
Vol 20 (87) ◽  
pp. 19-26 ◽  
Author(s):  
T.I. Stetsko ◽  
V.P. Muzyka ◽  
V.M. Hunchak
Keyword(s):  
Veterinary Medicine ◽  
Antimicrobial Resistance ◽  
Antimicrobial Therapy ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Animal Health ◽  
Point Of View ◽  
Animal Origin ◽  
European Medicines Agency ◽  
Antimicrobial Substances

The resistance of microorganisms, bacterial pathogens, to antimicrobials is a global problem in both healthcare and veterinary medicine. It is believed that the main reason for the emergence and spread of antimicrobial resistance in humans is the transfer of antibiotic resistant strains of microorganisms or genes, determinants of resistance, through products of animal origin from productive animals to humans. Thus, the main way of antimicrobial resistance containment is to restrain and minimize it through the prudent use of antibiotics in veterinary medicine, especially those that are critically important for productive animals. In addition, some classes of antibacterial substances and antibiotics, that are widely used in humane medicine, are used in veterinary medicine. The need to use and preserve these important therapeutic agents is relevant from the point of view of the concept «One Health». The article provides a list of all antibacterial substances used by productive animals for their importance in veterinary medicine, developed by a special group of experts of the World Organisation for Animal Health (OIE). Any antimicrobial agent authorized for use in veterinary medicine for productive animals, in accordance with the criteria for quality, safety and efficacy as defined in Section 6.9 of the Terrestrial Animal Health Code, is considered to be important for veterinary medicine. All the antimicrobial substances used for productive animals are divided in this list on critical, very important and important for veterinary medicine. Attention was also drawn to the peculiarities of the use of critical antimicrobial agents in veterinary medicine, especially those recognized as critical in humane medicine. These include aminoglycosides, cephalosporins of the 3rd and 4th generation, fluoroquinolones, glycopeptides, macrolides, some penicillins and polymyxins. The article also describes the classification of critical antimicrobials by the European Medicines Agency (EMA) and the Panel of Experts on Antimicrobials (AMEG) of the WHO based on the risk profile for humans through the development of antimicrobial resistance after application to productive animals. Such an assessment will give veterinary practitioners an important justification when they make decisions about the clinical treatment of bacterial infections and the responsible appointment of antimicrobial therapy. This will help to reach the balance among the achievement of the effectiveness of antimicrobial therapy of productive animals, reducing of the selective pressure on the development of antibiotic resistance and ensuring of a high level of human health.

scholarly journals Antimicrobial Resistance in Equine Reproduction

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3035
Author(s):  
Pongpreecha Malaluang ◽  
Elin Wilén ◽  
Johanna Lindahl ◽  
Ingrid Hansson ◽  
Jane M. Morrell
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Detrimental Effect ◽  
Antimicrobial Agents ◽  
Reproductive Tract ◽  
Sperm Quality ◽  
The United States ◽  
Critical Control Points ◽  
Background Exposure ◽  
Semen Extender

Bacteria develop resistance to antibiotics following low-level “background” exposure to antimicrobial agents as well as from exposure at therapeutic levels during treatment for bacterial infections. In this review, we look specifically at antimicrobial resistance (AMR) in the equine reproductive tract and its possible origin, focusing particularly on antibiotics in semen extenders used in preparing semen doses for artificial insemination. Our review of the literature indicated that AMR in the equine uterus and vagina were reported worldwide in the last 20 years, in locations as diverse as Europe, India, and the United States. Bacteria colonizing the mucosa of the reproductive tract are transferred to semen during collection; further contamination of the semen may occur during processing, despite strict attention to hygiene at critical control points. These bacteria compete with spermatozoa for nutrients in the semen extender, producing metabolic byproducts and toxins that have a detrimental effect on sperm quality. Potential pathogens such as Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa may occasionally cause fertility issues in inseminated mares. Antibiotics are added during semen processing, according to legislation, to impede the growth of these microorganisms but may have a detrimental effect on sperm quality, depending on the antimicrobial agent and concentration used. However, this addition of antibiotics is counter to current recommendations on the prudent use of antibiotics, which recommend that antibiotics should be used only for therapeutic purposes and after establishing bacterial sensitivity. There is some evidence of resistance among bacteria found in semen samples. Potential alternatives to the addition of antibiotics are considered, especially physical removal separation of spermatozoa from bacteria. Suggestions for further research with colloid centrifugation are provided.

scholarly journals Staphylococcus aureus biofilm and the role of bacteriophages in its eradication

2018 ◽  
Vol 72 ◽  
pp. 101-107
Author(s):  
Natalia Łubowska ◽  
Lidia Piechowicz
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Methicillin Resistance ◽  
Therapeutic Option ◽  
Resistant Bacteria ◽  
Prosthetic Heart Valves ◽  
Biofilm Structure ◽  
Implanted Devices

The ability to form biofilm is an important virulence factor of many microorganisms. Infections involving biofilms account for approx. 65% of all human infections. Biofilms may develop on intravascular catheters or implanted devices such as prosthetic heart valves. Implanted devices are covered by biofilm and become reservoirs of microorganisms which can be a cause of persistent infections (endocarditis, deep tissue abscesses, septic arthritis, and osteomyelitis). Treatment of infections caused by biofilm-growing cells is linked to a high risk of failure due to an extreme resistance to antimicrobial agents and increased capacity to evade the immune responses. A large number of biofilm-associated infections involve Staphylococcus aureus. Treatment of staphylococcal infections is a great challenge for clinicians because of the presence of various mechanisms of resistance to antibiotics in S. aureus, for example methicillin resistance and biofilm production. Therapeutic difficulties related with antibiotic-resistant bacteria and limitations in research on new antimicrobials were the reasons that nearly 100 years after discovery, bacteriophages caught the attention of scientists around the world as a new therapeutic option for bacterial infections. Numerous in vitro studies on S. aureus strains showed that phages can both prevent biofilm formation and contribute to the elimination of bacteria from the mature biofilm structure. The major role in biofilm eradication play depolymerases produced by some phages which facilitate their penetration into the inner layers of biofilm by disturbing the biofilm structure. This leads to the conclusion that bacteriophages treatment might become a new strategy in the prevention and eradication of infectious bacterial biofilms, including these formed by S. aureus.

scholarly journals Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

scholarly journals Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (5) ◽  
pp. 639 ◽  
Author(s):  
Alexis Simons ◽  
Kamel Alhanout ◽  
Raphaël E. Duval
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Further Development

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

Antimicrobial Resistance in the Intensive Care Unit

2016 ◽  
Vol 32 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Shawn H. MacVane
Keyword(s):  
Intensive Care ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Hospital Costs ◽  
High Morbidity ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Negative Organisms

Bacterial infections are a frequent cause of hospitalization, and nosocomial infections are an increasingly common condition, particularly within the acute/critical care setting. Infection control practices and new antimicrobial development have primarily focused on gram-positive bacteria; however, in recent years, the incidence of infections caused by gram-negative bacteria has risen considerably in intensive care units. Infections caused by multidrug-resistant (MDR) gram-negative organisms are associated with high morbidity and mortality, with significant direct and indirect costs resulting from prolonged hospitalizations due to antibiotic treatment failures. Of particular concern is the increasing prevalence of antimicrobial resistance to β-lactam antibiotics (including carbapenems) among Pseudomonas aeruginosa and Acinetobacter baumannii and, recently, among pathogens of the Enterobacteriaceae family. Treatment options for infections caused by these pathogens are limited. Antimicrobial stewardship programs focus on optimizing the appropriate use of currently available antimicrobial agents with the goals of improving outcomes for patients with infections caused by MDR gram-negative organisms, slowing the progression of antimicrobial resistance, and reducing hospital costs. Newly approved treatment options are available, such as β-lactam/β-lactamase inhibitor combinations, which significantly extend the armamentarium against MDR gram-negative bacteria.

scholarly journals Antimicrobial and Antibiofilm Activities of Essential Oils against Escherichia coli O157:H7 and Methicillin-Resistant Staphylococcus aureus (MRSA)

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 730
Author(s):  
Nicolás Gómez-Sequeda ◽  
Marlon Cáceres ◽  
Elena E. Stashenko ◽  
William Hidalgo ◽  
Claudia Ortiz
Keyword(s):  
Staphylococcus Aureus ◽  
Essential Oils ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Biological Activities ◽  
Antibiofilm Activity ◽  
Methicillin Resistant ◽  
E Coli ◽  
Microbial Infections

The emergence of multidrug resistant microorganisms represents a global challenge due to the lack of new effective antimicrobial agents. In this sense, essential oils (EOs) are an alternative to be considered because of their anti-inflammatory, antiviral, antibacterial, and antibiofilm biological activities. Therefore, multiple efforts have been made to consider the potential use of EOs in the treatment of infections which are caused by resistant microorganisms. In this study, 15 EOs of both Colombian and introduced aromatic plants were evaluated against pathogenic strains of E. coli O157:H7 and methicillin resistant Staphylococcus aureus (MRSA) in planktonic and sessile states in order to identify relevant and promising alternatives for the treatment of microbial infections. Forty different compounds were identified in the 15 EO with nine of them constituted mainly by oxygenated monoterpenes (OM). EOs from Lippia origanoides, chemotypes thymol, and carvacrol, displayed the highest antibacterial activity against E. coli O157:H7 (MIC50 = 0.9 and 0.3 mg/mL, respectively) and MRSA (MIC50 = 1.2 and 0.6 mg/mL, respectively). These compounds from EOs had also the highest antibiofilm activity (inhibition percentage > 70.3%). Using scanning electron microscopy (SEM), changes in the size and morphology of both bacteria were observed when they were exposed to sub-inhibitory concentrations of L. origanoides EO carvacrol chemotype. EOs from L. origanoides, thymol, and carvacrol chemotypes represented a viable alternative for the treatment of microbial infections; however, the Selectivity Index (SI ≤ 3) indicated that it was necessary to study alternatives to reduce its in vitro cytotoxicity.

scholarly journals Plant Derived Natural Products against Pseudomonas aeruginosa and Staphylococcus aureus: Antibiofilm Activity and Molecular Mechanisms

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5024
Author(s):  
Francesca Guzzo ◽  
Monica Scognamiglio ◽  
Antonio Fiorentino ◽  
Elisabetta Buommino ◽  
Brigida D’Abrosca
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Natural Products ◽  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Antibiofilm Activity ◽  
Complex Structures ◽  
Skin Infections ◽  
Human Pathogens ◽  
And Staphylococcus Aureus

Bacteria are social organisms able to build complex structures, such as biofilms, that are highly organized surface-associated communities of microorganisms, encased within a self- produced extracellular matrix. Biofilm is commonly associated with many health problems since its formation increases resistance to antibiotics and antimicrobial agents, as in the case of Pseudomonas aeruginosa and Staphylococcus aureus, two human pathogens causing major concern. P. aeruginosa is responsible for severe nosocomial infections, the most frequent of which is ventilator-associated pneumonia, while S. aureus causes several problems, like skin infections, septic arthritis, and endocarditis, to name just a few. Literature data suggest that natural products from plants, bacteria, fungi, and marine organisms have proven to be effective as anti-biofilm agents, inhibiting the formation of the polymer matrix, suppressing cell adhesion and attachment, and decreasing the virulence factors’ production, thereby blocking the quorum sensing network. Here, we focus on plant derived chemicals, and provide an updated literature review on the anti-biofilm properties of terpenes, flavonoids, alkaloids, and phenolic compounds. Moreover, whenever information is available, we also report the mechanisms of action.

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