Pentapeptide repeat protein QnrB1 requires ATP hydrolysis to rejuvenate poisoned gyrase complexes.

DNA gyrase, a type II topoisomerase found predominantly in bacteria, is the target for a variety of 'poisons', namely natural product toxins (e.g. albicidin, microcin B17) and clinically important synthetic molecules (e.g. fluoroquinolones). Resistance to both groups can be mediated by pentapeptide repeat proteins (PRPs). Despite long-term studies, the mechanism of action of these protective PRPs is not known. We show that a PRP, QnrB1 provides specific protection against fluoroquinolones, which strictly requires ATP hydrolysis by gyrase. QnrB1 binds to the GyrB protein and stimulates ATPase activity of the isolated N-terminal ATPase domain of GyrB (GyrB43). We probed the QnrB1 binding site using site-specific incorporation of a photoreactive amino acid and mapped the crosslinks to the GyrB43 protein. We propose a model in which QnrB1 binding allosterically promotes dissociation of the fluoroquinolone molecule from the cleavage complex.

Silk Sericin and Its Effect on Skin Wound Healing: A State of the Art.

Despite the significant progress in wound healing, chronic skin wounds remain a challenge for today's medicine. Due to the growing popularity of natural materials, silk protein-based dressings are gaining more attention in this field. Most studies refer to silk fibroin because sericin has been considered a waste product for years. However, sericin is also worth noting. Sericin-based dressings are mainly studied in cell cultures or animals. Sericin is the dressings' main component or can be included in more complex, advanced biomaterials. Recent studies highlight sericin's important role, noting its biocompatibility, biodegradability, and beneficial effects in skin wound healing, such as antibacterial activity, antioxidant and anti-inflammatory effects, or angiogenic properties. Developing sericin-based biomaterials is often simple, free of toxic by-products, and inexpensive, requiring no highly sophisticated apparatus. As a result, sericin-based dressings can be widely used in wound healing and have low environmental impact. However, the literature in this area is further limited. The following review collects and describes recent studies showing silk sericin's influence on skin wound healing.

Molecular mechanism of topoisomerase poisoning by the peptide antibiotic albicidin.

The peptide antibiotic albicidin is a DNA topoisomerase inhibitor with low-nanomolar bactericidal activity towards fluoroquinolone-resistant Gram-negative pathogens. However, its mode of action is poorly understood. We determined a 2.6 Å resolution cryoelectron microscopy structure of a ternary complex between Escherichia coli topoisomerase DNA gyrase, a 217 bp double-stranded DNA fragment and albicidin. Albicidin employs a dual binding mechanism where one end of the molecule obstructs the crucial gyrase dimer interface, while the other intercalates between the fragments of cleaved DNA substrate. Thus, albicidin efficiently locks DNA gyrase, preventing it from religating DNA and completing its catalytic cycle. Two additional structures of this trapped state were determined using synthetic albicidin analogues that demonstrate improved solubility, and activity against a range of gyrase variants and E. coli topoisomerase IV. The extraordinary promiscuity of the DNA-intercalating region of albicidins and their excellent performance against fluoroquinolone-resistant bacteria holds great promise for the development of last-resort antibiotics.

Beneficial Effect of Wound Dressings Containing Silver and Silver Nanoparticles in Wound Healing-From Experimental Studies to Clinical Practice.

Impaired wound healing affects hundreds of million people around the world; therefore, chronic wounds are a major problem not only for the patient, but also for already overloaded healthcare systems. Chronic wounds are always very susceptible to infections. Billions of dollars are spent to discover new antibiotics as quickly as possible; however, bacterial resistance against antibiotics is rising even faster. For this reason, a complete shift of the antibacterial treatment paradigm is necessary. The development of technology has allowed us to rediscover well-known agents presenting antimicrobial properties with a better outcome. In this context, silver nanoparticles are a promising candidate for use in such therapy. Silver has many useful properties that can be used in the treatment of chronic wounds, such as anti-bacterial, anti-inflammatory, and anti-oxidative properties. In the form of nanoparticles, silver agents can work even more effectively and can be more easily incorporated into various dressings. Silver-based dressings are already commercially available; however, innovative combinations are still being discovered and very promising results have been described. In this review article, the authors focused on describing experimental and clinical studies exploring dressings containing either silver or silver nanoparticles, the results of which have been published in recent years.

Silk Fibroin Biomaterials and Their Beneficial Role in Skin Wound Healing.

The skin, acting as the outer protection of the human body, is most vulnerable to injury. Wound healing can often be impaired, leading to chronic, hard-to-heal wounds. For this reason, searching for the most effective dressings that can significantly enhance the wound healing process is necessary. In this regard, silk fibroin, a protein derived from silk fibres that has excellent properties, is noteworthy. Silk fibroin is highly biocompatible and biodegradable. It can easily make various dressings, which can be loaded with additional substances to improve healing. Dressings based on silk fibroin have anti-inflammatory, pro-angiogenic properties and significantly accelerate skin wound healing, even compared to commercially available wound dressings. Animal studies confirm the beneficial influence of silk fibroin in wound healing. Clinical research focusing on fibroin dressings is also promising. These properties make silk fibroin a remarkable natural material for creating innovative, simple, and effective dressings for skin wound healing. In this review, we summarise the application of silk fibroin biomaterials as wound dressings in full-thickness, burn, and diabetic wounds in preclinical and clinical settings.

Comparison of transcatheter aortic valve implantation outcomes in patients younger than 85 years and those aged 85 years or older: a single-center study.

INTRODUCTION: The number of elderly patients requiring treatment of aortic stenosis is expected to grow steadily due to increasing lifespan. Transcatheter aortic valve implantation (TAVI) is an alternative treat­ ment for patients with aortic stenosis considered nonoptimal candidates for surgical valve replacement. OBJECTIVES: We aimed to assess age­related differences in 30­day and 1­year cardiovascular mortality, Valve Academic Research Consortium­2 (VARC­2)-defined complications in patients undergoing TAVI, by comparing outcomes in patients younger than 85 years and those aged 85 years or older. PATIENTS AND METHODS: The study group included patients who underwent TAVI at the Institute of Cardiology, Warsaw from January 2009 to July 2019. Clinical, procedural, and follow­up data were retrospectively collected and compared in 2 groups defined according to age: group 1, younger than 85 years (417) and group 2, aged 85 or older (200). RESULTS: The surgical risk profile assessed by the EuroSCORE II was significantly higher in the group of older patients (median [interquartile range], 6.5% [3.5%-17.3%] vs 7.2% [3.4%-18.1%]; P = 0.002); 30­day and 1­year cardiovascular mortality was 4.3% in group 1 as compared with 5% in group 2 (P = 0.69) and 10.8% in group 1 as compared with 9.4% in group 2 (P = 0.51), respectively. The rate of VARC­2­defined complications was similar in both groups, with the exception of major vascular com­ plications (3.12% vs 8.5%; P = 0.004) and major bleeding (10.8% vs 18.5%; P = 0.008), which were more prevalent in older patients. CONCLUSION: Cardiovascular mortality at 1 month and 1 year following TAVI is similar in patients aged 85 years or older and in those younger than 85 years.

Epizootic Situation of Feline Bartonella Infection in Eastern Poland.

INTRODUCTION: The aim of the study was to establish the prevalence of Bartonella spp. in cats in eastern Poland, and to determine the factors associated with the infection. MATERIAL AND METHODS: PCRs were performed to detect Bartonella DNA in the whole blood of 672 cats from four regions in eastern Poland (the Lublin, Podlasie, Masovian, and Subcarpathian provinces). The association between the previously selected variables and the dependent variable (presence of Bartonella DNA) was investigated using a logistic regression model. RESULTS: The overall prevalence of infection was 40.48%. All PCR positive cats were infected with B. henselae. The living conditions of the animals (free outdoor roaming), mixed breed cats, Subcarpathian region, and absence of tick control were significant risk factors associated with Bartonella infection at a 95% confidence level. CONCLUSION: Cats in eastern Poland appear to be at risk of a bartonellosis epizootic. Factors which seem to impact the likelihood of infection in cats and factors which seem not to impact it have been suggested. We advocate additional research into the ways bartonellosis spreads, its geographical scope, and the factors that favour its development.

Myocarditis secondary to Borrelia infection in a dog: a case report.

The aim of this study was to recognise the etiological factor of a disease with symptoms of lameness and cardiac failure, which occurred in one dog 4 weeks after invasion by ticks. A serological examination as well as molecular examination (PCR) was done. In the sample of the serum, the presence of antibodies specific to Borrelia burgdorferi were detected. Antibiotic therapy with doxycycline did not cause significant improvement, so the owners of the dog decided about its euthanasia. During the necroscopy, a dilated heart was recognised. In the heart samples, the genetic material of Borrelia was detected. The results of serological and molecular examinations showed that in the discussed case, an etiological factor of the disease was spirochetes. In light of the research, veterinary practitioners should keep in mind the presence of Lyme disease in dogs in Poland and include it in differential diagnoses for lameness and cardiological problems.

Cats as a reservoir of Bartonella henselae for dogs.

Bartonellosis is a disease affecting a variety of animals. Many Bartonella infections are zoonotic, including cat scratch disease. Within the genus Bartonella are 45 species, of which more than 10 can infect cats and dogs. Companion animals serve as reservoirs for several zoonotic species of Bartonella, and may also serve as sentinels for zoonotic Bartonella species harbored by wildlife. The aim of this study was to determine the frequency of the occurrence of Bartonella spp. DNA in dogs from households where cats with clinical bartonellosis were kept. The presence of DNA with 99-100% compliance of the nucleotide sequence with the sequence of the Bartonella DNA isolated from cats was demonstrated in the body of 10% of tested dogs. The results indicate that cats serve as a Bartonella reservoir for dogs, and the dogs can play the same role with regard to humans.

Properties of capsaicin and its utility in veterinary and human medicine.

The main aim of this paper was to show the variety of capsaicin's properties. Capsaicin is an active component of plants of the Capsicum genus, and is known for its pungency. Capsaicin is used in the food, pharmaceutical and cosmetic industries. Additional properties of capsaicin have been demonstrated, including pain relief, weight loss, body thermoregulation, and antioxidant, antimicrobial and anticancer activities. Studies of capsaicin's effects on the human and animal organism need to be continued, with special emphasis on new applications.

Feline bartonellosis key issues and possible vectors

Bartonellosis is a disease caused by Bartonella spp. microorganisms which belong to the Rickettsiales order. This disease is a zoonosis, B. henselae, whose primary reservoir is the cat, which in humans causes a cat-scratch disease. In infected cats, symptoms such as fever, lymphedema, reproduction disorders, myocarditis, rhinotracheitis, gingivitis, and arthritis may be observed. Bartonella appears to be transmitted among cats and dogs in vivo exclusively by arthropod vectors (excepting perinatal transmission), not by biting or scratching. In the absence of these vectors, the disease does not spread. On the other hand, the disease can be spread to humans by bites and scratches, and it is highly likely that it is spread by arthropod vectors as well. This review presents a potential role of ticks and fleas in the transmission of bartonellosis. Clinicians should be aware that a common illness, such as infection with Bartonella, can be transmitted by arthropod vectors, and that a history of animal scratches or bites is not necessary for disease transmission.

A peptide factor secreted by Staphylococcus pseudintermedius exhibits properties of both bacteriocins and virulence factors.

Staphylococcus pseudintermedius is a common commensal bacterium colonizing the skin and mucosal surfaces of household animals. However, it has recently emerged as a dangerous opportunistic pathogen, comparable to S. aureus for humans. The epidemiological situation is further complicated by the increasing number of methicillin-resistant S. pseudintermedius infections and evidence of gene transmission driving antibiotic resistance between staphylococci colonizing human and zoonotic hosts. In the present study, we describe a unique peptide, BacSp222, that possesses features characteristic of both bacteriocins and virulence factors. BacSp222 is secreted in high quantities by S. pseudintermedius strain 222 isolated from dog skin lesions. This linear, fifty-amino-acid highly cationic peptide is plasmid-encoded and does not exhibit significant sequence similarities to any other known peptides or proteins. BacSp222 kills gram-positive bacteria (at doses ranging from 0.1 to several micromol/l) but also demonstrates significant cytotoxic activities towards eukaryotic cells at slightly higher concentrations. Moreover, at nanomolar concentrations, the peptide also possesses modulatory properties, efficiently enhancing interferon gamma-induced nitric oxide release in murine macrophage-like cell lines. BacSp222 appears to be one of the first examples of multifunctional peptides that breaks the convention of splitting bacteriocins and virulence factors into two unrelated groups.