Smart Chimeric Lysin ClyC Loaded Alginate Hydrogel Reduces Staphylococcus aureus Induced Bone Infection

Staphylococcus aureus (S. aureus) is the most common cause of hospital and community-acquired infections. The current clinical treatment is limited by the emergence of drug-resistant strains. We previously developed a chimeric ClyC that effectively inhibited S. aureus strains. Nonetheless, an efficient delivery system to provide sustained release of ClyC to infected site is needed. Thus, we engineered a chimeric ClyC loaded alginate hydrogel (ClyC-AH) to improve the therapeutic outcomes against S. aureus. ClyC-AH retained the stability and activity of ClyC while providing a sustained release of ClyC and a continuous antibacterial effect against S. aureus. Compared to ClyC alone, the use of ClyC-AH was relatively safe, as there was no significant cytotoxicity to BHK-21 cells at a ClyC concentration≤250 μg/ml. Furthermore, in a S. aureus infected mouse model of osteomyelitis, ClyC-AH reduced bacterial burden in the femur and surrounding tissues, with a reduction of 2 log10 (CFU/ml) in viable bacterial number. Based on these results, hydrogel-delivered chimeric lysin ClyC provides a promising future in the S.aureus targeting therapy.

Download Full-text

Effects of Tormentic Acid and the Extracts from Callistemon citrinus on the Production of Extracellular Proteases by Staphylococcus aureus

Biochemistry Research International ◽

10.1155/2020/6926320 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Rumbidzai Mashezha ◽

Molly Mombeshora ◽

Stanley Mukanganyama

Keyword(s):

Staphylococcus Aureus ◽

Ethanol Extract ◽

Extracellular Protease ◽

Protease Production ◽

Extracellular Proteases ◽

Therapeutic Molecules ◽

Antibacterial Susceptibility ◽

Resistant Strains ◽

Drug Resistant Strains ◽

Tormentic Acid

Staphylococcus aureus is among the common nosocomial pathogens. Antibiotics have been used to treat S. aureus infections. However, there has been increased mortality associated with drug-resistant strains of S. aureus. Extracellular proteases have been implicated to be responsible for the transition of S. aureus from an adhesive pathogen to an invasive pathogen. The development of resistant strains has necessitated the search for new sources of drugs. Plants have been traditionally used as sources of therapeutic molecules. The objective of this study was to determine the effect of tormentic acid and the extracts from Callistemon citrinus on the production of extracellular proteases by S. aureus. The broth microdilution antibacterial susceptibility assay was used to determine the antibacterial effects of tormentic acid and the extracts on S. aureus. Both extracts showed a minimum inhibitory concentration (MIC) value of 50 μg/ml. The water : ethanol (50 : 50) and the dichloromethane : methanol (50 : 50) extracts were found to be bactericidal against S. aureus at a concentration of 100 μg/ml and 50 μg/ml, respectively. The effect of tormentic acid and extracts on extracellular protease production was investigated using the protease assay. A zone of proteolytic activity (Pr) was measured as the ratio of the diameter of the colony to the total diameter of colony plus zone of hydrolysis. The extracts reduced the production of extracellular proteases, while tormentic acid completely inhibited the production of extracellular proteases by S. aureus. The Pr value for tormentic acid was found to be 1. The Pr values of the dichloromethane : methanol extract and the water : ethanol extract were 0.92 and 0.84, respectively. In conclusion, tormentic acid was shown to inhibit extracellular protease production; therefore, there is need to explore its use in antivirulence therapy to combat S. aureus infections.

Download Full-text

Staphylococcus aureus vaccines: Deviating from the carol

Journal of Experimental Medicine ◽

10.1084/jem.20160569 ◽

2016 ◽

Vol 213 (9) ◽

pp. 1645-1653 ◽

Cited By ~ 44

Author(s):

Dominique Missiakas ◽

Olaf Schneewind

Keyword(s):

Staphylococcus Aureus ◽

Protein A ◽

Invasive Disease ◽

Phagocytic Cells ◽

Subunit Vaccines ◽

Clinical Endpoints ◽

Patients At Risk ◽

Resistant Strains ◽

Opsonophagocytic Killing ◽

Drug Resistant Strains

Staphylococcus aureus, a commensal of the human nasopharynx and skin, also causes invasive disease, most frequently skin and soft tissue infections. Invasive disease caused by drug-resistant strains, designated MRSA (methicillin-resistant S. aureus), is associated with failure of antibiotic therapy and elevated mortality. Here we review polysaccharide-conjugate and subunit vaccines that were designed to prevent S. aureus infection in patients at risk of bacteremia or surgical wound infection but failed to reach their clinical endpoints. We also discuss vaccines with ongoing trials for combinations of polysaccharide-conjugates and subunits. S. aureus colonization and invasive disease are not associated with the development of protective immune responses, which is attributable to a large spectrum of immune evasion factors. Two evasive strategies, assembly of protective fibrin shields via coagulases and protein A–mediated B cell superantigen activity, are discussed as possible vaccine targets. Although correlates for protective immunity are not yet known, opsonophagocytic killing of staphylococci by phagocytic cells offers opportunities to establish such criteria.

Download Full-text

ANTIBACTERIAL ACTIVITY OF BIOSYNTHESIZED SILVER NANOPARTICLES FROM VIOLA SERPENS AGAINST MULTI DRUG RESISTANT STRAINS OF STAPHYLOCOCCUS AUREUS AND PSEUDOMONAS AERUGINOSA

World Journal of Pharmaceutical Research ◽

10.20959/wjpr20178-8994 ◽

2017 ◽

pp. 1379-1393

Author(s):

Anu Kumar

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Silver Nanoparticles ◽

Antibacterial Activity ◽

Drug Resistant ◽

Resistant Strains ◽

Drug Resistant Strains

Download Full-text

Comparative Analysis of Common and Unique Targets in Drug Resistant Strains of Staphylococcus aureus

Frontier Discoveries and Innovations in Interdisciplinary Microbiology ◽

10.1007/978-81-322-2610-9_12 ◽

2016 ◽

pp. 193-205

Author(s):

Amandeep Kaur Kahlon ◽

Mahendra P. Darokar ◽

Ashok Sharma

Keyword(s):

Staphylococcus Aureus ◽

Comparative Analysis ◽

Drug Resistant ◽

Resistant Strains ◽

Drug Resistant Strains

Download Full-text

Studies on the effects of 3-acetyl-4"-isovaleryltylosin against multiple-drug resistant strains of Staphylococcus aureus.

The Journal of Antibiotics ◽

10.7164/antibiotics.34.305 ◽

1981 ◽

Vol 34 (3) ◽

pp. 305-312 ◽

Cited By ~ 7

Author(s):

MASAMI TSUCHIYA ◽

KAYOKO SUZUKAKE ◽

MAKOTO HORI ◽

TSUTOMU SAWA ◽

TOMIO TAKEUCHI ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Multiple Drug ◽

Drug Resistant ◽

Multiple Drug Resistant ◽

Resistant Strains ◽

Drug Resistant Strains

Download Full-text

Recombinant ESAT-6-Like Proteins Provoke Protective Immune Responses against Invasive Staphylococcus aureus Disease in a Murine Model

Infection and Immunity ◽

10.1128/iai.02498-14 ◽

2014 ◽

Vol 83 (1) ◽

pp. 339-345 ◽

Cited By ~ 15

Author(s):

Bao Zhong Zhang ◽

Yan Hong Hua ◽

Bin Yu ◽

Candy Choi Yi Lau ◽

Jian Piao Cai ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Immune Responses ◽

Survival Rates ◽

Passive Immunization ◽

Health Concern ◽

Drug Resistant ◽

Public Health Concern ◽

Content Type ◽

Resistant Strains ◽

Drug Resistant Strains

Staphylococcus aureusis a common pathogen found in the community and in hospitals. Most notably, methicillin-resistantS. aureusis resistant to many antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments, such as immunotherapeutic approaches. To date, most clinical trials of vaccines or of passive immunization againstS. aureushave ended in failure. In this study, we investigated two ESAT-6-like proteins secreted byS. aureus,S. aureusEsxA (SaEsxA) and SaEsxB, as possible targets for a vaccine. Mice vaccinated with these purified proteins elicited high titers of anti-SaEsxA and anti-SaEsxB antibodies, but these antibodies could not preventS. aureusinfection. On the other hand, recombinant SaEsxA (rSaEsxA) and rSaEsxB could induce Th1- and Th17-biased immune responses in mice. Mice immunized with rSaEsxA and rSaEsxB had significantly improved survival rates when challenged withS. aureuscompared with the controls. These findings indicate that SaEsxA and SaEsxB are two promising Th1 and Th17 candidate antigens which could be developed into multivalent and serotype-independent vaccines againstS. aureusinfection.

Download Full-text

Study of bacterial pathogens causing chronic suppurative otitis media and the antibiotic susceptibility pattern of the isolates at a tertiary care centre in Kochi

International Journal of Otorhinolaryngology and Head and Neck Surgery ◽

10.18203/issn.2454-5929.ijohns20201288 ◽

2020 ◽

Vol 6 (4) ◽

pp. 714

Author(s):

Geetha Nair ◽

Tanya Tonny Mampilly ◽

Bindhu Vasudevan ◽

J. Lancy

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Otitis Media ◽

Tertiary Care ◽

Drug Resistant ◽

Care Centre ◽

Tertiary Care Centre ◽

Suppurative Otitis Media ◽

Resistant Strains ◽

Drug Resistant Strains

Background: Chronic suppurative otitis media (CSOM) is defined as chronic inflammation of middle ear and mastoid cavity presenting with recurrent ear discharges through a tympanic membrane perforation. Complications of CSOM were frequent in pre-antibiotic era. Injudicious use of antibiotics led to the emergence of multi-drug resistant strains and complications in return. To isolate the organisms associated with CSOM in a tertiary care centre and to detect their antibiogram.Methods: In this clinical, prospective, cross sectional study, a total of 100 patients clinically diagnosed with CSOM were enrolled from January to December 2019 (1 year). Results: Of the 100 samples collected, predominant bacteria were isolated in 58 patients (58%). The most common isolate was Pseudomonas aeruginosa (29 isolates) followed by Staphylococcus aureus (24), Klebsiella species (3) and 1 isolate each of Pneumococci and Acinetobacter species. Among the 29 isolates of Pseudomonas aeruginosa, 8 (28%) were multidrug resistant. Sensitivity was 100% to imipenem followed by 97% to meropenem,79% to gentamicin, 76% to amikacin, 66% to ciprofloxacin, 41% to piperacillin tazobactam and 17% to ceftazidime. Of the 24 isolates of Staphylococcus aureus, 4 (16%) were methicillin resistant Staphylococcus aureus (MRSA).Conclusions: Pseudomonas aeruginosa was the most common isolate, of which 28% were multi drug resistant. This calls for the judicious use of antibiotics and alternative measures for treatment of drug resistant strains. Formulating an antibiotic policy based on the local antibiogram can help in preventing the emergence and spread of resistant pathogens.

Download Full-text

Vancomycin intermediate resistant Staphylococcus aureus in the nasal cavity of asymptomatic individuals: a potential public health challenge

African Health Sciences ◽

10.4314/ahs.v20i3.12 ◽

2020 ◽

Vol 20 (3) ◽

pp. 1109-1117

Author(s):

Morenike Adeoye-Isijola ◽

Olufunmiso Olajuyigbe ◽

Kehinde Adebola ◽

Roger Coopoosamy ◽

Anthony Afolayan

Keyword(s):

Staphylococcus Aureus ◽

Multidrug Resistant ◽

Multi Drug Resistance ◽

Agar Dilution ◽

Public Health Challenge ◽

Resistant Strains ◽

Inhibition Zones ◽

Asymptomatic Individuals ◽

Drug Resistant Strains ◽

Potential Public Health

Background: The potential of transmitting multidrug resistant Staphylococcus aureus from asymptomatic individuals to healthy individuals could constitute a great challenge to antimicrobial therapy. Methods: The antibiograms of the S. aureus from asymptomatic individuals were determined by disk diffusion and agar dilution assay techniques with different antibiotics and vancomycin. Results: Of the 152 S. aureus isolated, (59)38.8% isolates were multi-drug resistant strains. Streptomycin was the most effective and inhibited (135)88.82% of the isolates while ceftazidime inhibited (24)15.8% of the isolates. While (82)54.0% of the isolates inhibited by cefuroxime had resistant colonies within their inhibition zones (Rc) and ofloxacin inhibited (100)65.8% of the isolates without having resistant colonies within the inhibition zones, ceftazidime inhibited (7)4.6% of the isolates with resistant colonies within the inhibition zones. Subjecting the isolates to vancomycin showed that (27)17.8% were resistant to 2 µg/ml, (43)28.3% were resistant to 4 µg/ml and (27)17.8% of the isolates were simultaneously resistant to both concentrations of vancomycin. Although (100)65.8% of the isolates had MARindex ≥0.2, (52)34.2% of the isolates had MARindex ≤ 0.2 and (65)428% of the isolates were considered multidrug resistant strains. Conclusion: The isolation of multi-drug and vancomycin intermediate resistant strains of S. aureus in high percentage, in this study, presents a great threat to clinicians and general populace. The vancomycin intermediate resistant S. aureus (VISA) in asymptomatic individuals could be a critical concern to the therapeutic dilemma to be added to the presence of multi-drug resistance. A more sustainable therapy must be in place to prevent its dissemination or the outbreak of its infection. Keywords: Antibacterial activity; multidrug resistance; VRSA; VISA; vancomycin

Download Full-text

Antibiotic resistance is lower in Staphylococcus aureus isolated from antibiotic-free raw meat as compared to conventional raw meat

10.1101/448209 ◽

2018 ◽

Author(s):

Haskell Kyler J. ◽

Schriever Samuel R. ◽

Fonoimoana Kenisi D. ◽

Haws Benjamin ◽

Hair Bryan B. ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Meat Products ◽

Human Consumption ◽

Raw Meat ◽

Resistance Selection ◽

Poultry Products ◽

Frequent Use ◽

Resistant Strains ◽

Drug Resistant Strains

AbstractThe frequent use of antibiotics contributes to antibiotic resistance in bacteria, resulting in an increase in infections that are difficult to treat. Livestock are commonly administered antibiotics in their feed, but there is current interest in raising animals that are only administered antibiotics during active infections. Staphylococcus aureus (SA) is a common pathogen of both humans and livestock raised for human consumption. SA has achieved high levels of antibiotic resistance, but the origins and locations of resistance selection are poorly understood. We determined the prevalence of SA and MRSA in conventional and antibiotic-free (AF) meat products, and also measured rates of antibiotic resistance in these isolates. We isolated SA from raw conventional turkey, chicken, beef, and pork samples and also from AF chicken and turkey samples. We found that SA contamination was common, with an overall prevalence of 22.64% (range of 2.78-30.77%) in conventional meats and 13.0% (range of 12.5-13.2%) in AF poultry meats. MRSA was isolated from 15.72% of conventional raw meats (range of 2.78-20.41%) but not from AF-free meats. The degree of antibiotic resistance in conventional poultry products was significantly higher vs AF poultry products for a number of different antibiotics, and while multi-drug resistant strains were relatively common in conventional meats none were detected in AF meats. The use of antibiotics in livestock contributes to high levels of antibiotic resistance in SA found in meat products. Our results support the use of AF conditions for livestock in order to prevent antibiotic resistance development in SA.

Download Full-text