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Microbiology and Molecular Biology... Jun 2023Clinical management of Staphylococcus aureus infections presents a challenge due to the high incidence, considerable virulence, and emergence of drug resistance... (Review)
Review
Clinical management of Staphylococcus aureus infections presents a challenge due to the high incidence, considerable virulence, and emergence of drug resistance mechanisms. The treatment of drug-resistant strains, such as methicillin-resistant S. aureus (MRSA), is further complicated by the development of tolerance and persistence to antimicrobial agents in clinical use. To address these challenges, membrane disruptors, that are not generally considered during drug discovery for agents against S. aureus, should be explored. The cell membrane protects S. aureus from external stresses and antimicrobial agents, but membrane-targeting antimicrobial agents are probably less likely to promote bacterial resistance. Nontypical linear cationic antimicrobial peptides (AMPs), highly modified AMPs such as daptomycin (lipopeptide), bacitracin (cyclic peptide), and gramicidin S (cyclic peptide), are currently in clinical use. Recent studies have demonstrated that AMPs and small molecules can penetrate the cell membrane of S. aureus, inhibit phospholipid biosynthesis, or block the passage of solutes between the periplasm and the exterior of the cell. In addition to their primary mechanism of action (MOA) that targets the bacterial membrane, AMPs and small molecules may also impact bacteria through secondary mechanisms such as targeting the biofilm, and downregulating virulence genes of S. aureus. In this review, we discuss the current state of research into cell membrane-targeting AMPs and small molecules and their potential mechanisms of action against drug-resistant physiological forms of S. aureus, including persister cells and biofilms.
Topics: Humans; Staphylococcus aureus; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Antimicrobial Peptides; Anti-Infective Agents; Peptides, Cyclic; Cell Membrane; Biofilms; Staphylococcal Infections
PubMed: 37129495
DOI: 10.1128/mmbr.00037-22 -
The Journal of Physical Chemistry... Apr 2024Terahertz time-domain spectroscopy and differential scanning calorimetry were used to study the role of the dynamics of biomolecules decoupled from solvent effects....
Terahertz time-domain spectroscopy and differential scanning calorimetry were used to study the role of the dynamics of biomolecules decoupled from solvent effects. Lyophilized sucrose exhibited steadily increasing absorption with temperature as anharmonic excitations commenced as the system emerged from a deep minimum of the potential energy landscape where harmonic vibrations dominate. The polypeptide bacitracin and two globular proteins, lysozyme and human serum albumin, showed a more complex temperature dependence. Further analysis focused on the spectral signature below and above the boson peak. We found evidence of the onset of anharmonic motions that are characteristic for partial unfolding and molecular jamming in the dry biomolecules. The activation of modes of the protein molecules at temperatures comparable to the protein dynamical transition temperature was observed in the absence of hydration. No evidence of Fröhlich coherence, postulated to facilitate biological function, was found in our experiments.
Topics: Humans; Proteins; Solvents; Temperature; Water
PubMed: 38527099
DOI: 10.1021/acs.jpclett.3c03584 -
Ophthalmic Plastic and Reconstructive...Surgical fires pose a substantial risk to patients and can cause significant injury, especially in oculofacial surgery. Ocular surface lubricants can potentially act as...
PURPOSE
Surgical fires pose a substantial risk to patients and can cause significant injury, especially in oculofacial surgery. Ocular surface lubricants can potentially act as fuel for an operating room fire. We present an experimental analysis of the flammability of 9 commonly used ophthalmic lubricants under 4 ignition sources used in oculofacial surgery with and without supplemental oxygen.
METHODS
The flammability of 9 ophthalmic lubricants were tested under various operating room conditions. Each lubricant was exposed to 4 different ignition sources: an open flame lighter, monopolar cautery, bipolar cautery, and hand-held high temperature cautery, and the response of the lubricant was recorded. The testing was conducted both in room air and with 6 L/minute of 100% oxygen directed at the lubricant through a nasal cannula. Any reaction in which there was ignition, sparking, smoking, or a transient or permanent change in appearance of the lubricant was deemed notable.
RESULTS
Of the 9 lubricants tested, 4 displayed a reaction to the ignition source. Without supplemental oxygen, 100% petrolatum and neomycin-polysporin-bacitracin-hydrocortisone ointment produced some smoke when applied with the high temperature cautery. Notably, under both the conditions of no supplemental oxygen and with the addition of 6 L/minute of 100% oxygen, the carboxymethylcellulose drops and lidocaine jelly both conducted and sparked with the monopolar cautery leaving visible burn marks on the paper.
CONCLUSIONS
The overall fire hazard posed by ocular surface lubricants is low. Some topical lubricants can conduct electricity from monopolar cautery, which could increase the risk of inadvertent electrical burns. Certain lubricants could potentially become a fuel source when used in combination with hand-held high temperature battery cautery. Bipolar cautery was not associated with either increased conductivity or flammability with any of the lubricants tested.
Topics: Humans; Fires; Operating Rooms; Burns; Oxygen; Lubricants
PubMed: 37486341
DOI: 10.1097/IOP.0000000000002469 -
Microbial Pathogenesis Jun 2024It is common knowledge that prolonged and excessive use of antibiotics can lead to antimicrobial resistance. However, the characteristics and mechanism of...
It is common knowledge that prolonged and excessive use of antibiotics can lead to antimicrobial resistance. However, the characteristics and mechanism of resistant-bacteria induced by clinically recommended and prophylactic dose drugs remain largely unclear. This study aimed to observe the trends of drug resistance of the bacitracin-susceptible Staphylococcus aureus strain FS127 under exposure to bacitracin (BAC), which were induced in vitro and in chicken gut. Antimicrobial susceptibility testing was used to detect the susceptibility of S. aureus induced in vitro and in the chicken gut to gentamicin, chloramphenicol, tetracycline, doxycycline, penicillin and chloramphenicol. The research results showed that bacitracin could induce drug resistance in S. aureus both in vitro and in vivo. The bacitracin-resistance rate of S. aureus isolated from chicken gut was positively correlated with the dose and time of bacitracin administration. The findings revealed that bacitracin-resistant S. aureus induced in vivo had enhanced susceptibility to chloramphenicol but no such change in vitro. Meanwhile, RT-qPCR assay was used to detect the expression levels of vraD, braD, braR and bacA in typical strains with different bacitracin-resistance levels. It was found that BacA may play a key role in the bacitracin resistance of S. aureus. In conclusion, this work reveals the characteristics and mechanism of bacitracin-resistant S. aureus induced by bacitracin in vivo and in vitro respectively.
Topics: Bacitracin; Animals; Chickens; Staphylococcus aureus; Microbial Sensitivity Tests; Anti-Bacterial Agents; Drug Resistance, Bacterial; Staphylococcal Infections; Chloramphenicol; Gastrointestinal Tract; Bacterial Proteins
PubMed: 38685360
DOI: 10.1016/j.micpath.2024.106666 -
Critical Reviews in Analytical Chemistry Jun 2023Chiral separation techniques play a crucial role in the pharmaceutical industry, where the enantiomeric purity of drugs can have a significant impact on their efficacy... (Review)
Review
Chiral separation techniques play a crucial role in the pharmaceutical industry, where the enantiomeric purity of drugs can have a significant impact on their efficacy and safety. Macrocyclic antibiotics are highly effective chiral selectors used in various chiral separation techniques, including LC, HPLC, SMB, and TLC, offering reproducible results and a wide range of applications. However, developing robust and efficient immobilization mechanisms for these chiral selectors remains a challenge. This review article focuses on various immobilization approaches, such as immobilization, coating, encapsulation, and photosynthesis, that have been applied to immobilize macrocyclic antibiotics on their support. Commercially available macrocyclic antibiotics for conventional liquid chromatography include Vancomycin, Norvancomycin, Eremomycin, Teicoplanin, Ristocetin A, Rifamycin, Avoparcin, Bacitracin, and others. In addition, capillary (nano) liquid chromatography has also been used in chiral separation utilizing Vancomycin, Polymyxin B, Daptomycin, and Colistin Sulfate. Macrocyclic antibiotic-based CSPs have been extensively applied due to their reproducible results, ease of use, and broad range of applications, capable of separating a large number of racemates.
PubMed: 37342891
DOI: 10.1080/10408347.2023.2224442 -
Australian Endodontic Journal : the... Aug 2023The aim of this integrative review was to identify whether the disinfection procedures performed prior to regenerative endodontic treatment were effective on biofilm... (Review)
Review
The aim of this integrative review was to identify whether the disinfection procedures performed prior to regenerative endodontic treatment were effective on biofilm removal from the root canals. The research was based on PubMed, Latin American and Caribbean Health Sciences Literature (Lilacs) and Scientific Electronic Library Online (SciELO) databases. Four articles were selected; one of the studies was in vivo and the others ex vivo. Different disinfection procedures were studied, characterised mainly by the use of intracanal medication, highlighting the double antibiotic paste, triple antibiotic paste and calcium hydroxide paste. Disinfection ability was evaluated against Enterococcus faecalis and multispecies biofilms by using the fluorescence technique and colony forming unit counting, for 7 to 21 days. Double antibiotic paste and triple antibiotic paste demonstrated excellent antibiofilm activity, unlike CH paste that showed limited disinfection, even when associated with different antimicrobial agents. Triple antibiotic paste was the most effective medication against biofilm.
Topics: Disinfection; Regenerative Endodontics; Root Canal Irrigants; Anti-Bacterial Agents; Anti-Infective Agents; Bacitracin; Polymyxin B; Framycetin; Enterococcus faecalis; Calcium Hydroxide; Biofilms; Dental Pulp Cavity
PubMed: 35932453
DOI: 10.1111/aej.12670 -
Pharmaceutics Jul 2023produces several classes of antimicrobial substances, including bacteriocins, which are peptides or proteins with different structural composition and molecular mass:... (Review)
Review
produces several classes of antimicrobial substances, including bacteriocins, which are peptides or proteins with different structural composition and molecular mass: ribosomally synthesized by bacteria (1.4-20 kDa), non-ribosomally synthesized peptides and cyclic lipopeptides (0.8-42 kDa) and exopolysaccharides (>1000 kDa). Different bacteriocins act against Gram-positive or Gram-negative bacteria, fungal pathogens and amoeba cells. The main mechanisms of bacteriocin lytic activity include interaction of peptides with membranes of target cells resulting in structural alterations, pore-forming, and inhibition of cell wall biosynthesis. DNase and RNase activity for some bacteriocines are also postulated. Non-ribosomal peptides are synthesized by special non-ribosomal multimodular peptide synthetases and contain unnatural amino acids or fatty acids. Their harmful effect is due to their ability to form pores in biological membranes, destabilize lipid packaging, and disrupt the peptidoglycan layer. Lipopeptides, as biosurfactants, are able to destroy bacterial biofilms. Secreted polysaccharides are high molecular weight compounds, composed of repeated units of sugar moieties attached to a carrier lipid. Their antagonistic action was revealed in relation to bacteria, viruses, and fungi. Exopolysaccharides also inhibit the formation of biofilms by pathogenic bacteria and prevent their colonization on various surfaces. However, mechanism of the harmful effect for many secreted antibacterial substances remains unknown. The antimicrobial activity for most substances has been studied in vitro only, but some substances have been characterized in vivo and they have found practical applications in medicine and veterinary. The cyclic lipopeptides that have surfactant properties are used in some industries. In this review, special attention is paid to the antimycobacterials produced by as a possible approach to combat multidrug-resistant and latent tuberculosis. In particular, licheniformins and bacitracins have shown strong antimycobacterial activity. However, the medical application of some antibacterials with promising in vitro antimycobacterial activity has been limited by their toxicity to animals and humans. As such, similar to the enhancement in the antimycobacterial activity of natural bacteriocins achieved using genetic engineering, the reduction in toxicity using the same approach appears feasible. The unique capability of to synthesize and produce a range of different antibacterial compounds means that this organism can act as a natural universal vehicle for antibiotic substances in the form of probiotic cultures and strains to combat various types of pathogens, including mycobacteria.
PubMed: 37514078
DOI: 10.3390/pharmaceutics15071893 -
Journal of Peptide Science : An... Jun 2024The rise of antimicrobial resistance and multi-drug resistant pathogens has necessitated explorations for novel antibiotic agents as the discovery of conventional... (Review)
Review
The rise of antimicrobial resistance and multi-drug resistant pathogens has necessitated explorations for novel antibiotic agents as the discovery of conventional antibiotics is becoming economically less viable and technically more challenging for biopharma. Antimicrobial peptides (AMPs) have emerged as a promising alternative because of their particular mode of action, broad spectrum and difficulty that microbes have in becoming resistant to them. The AMPs bacitracin, gramicidin, polymyxins and daptomycin are currently used clinically. However, their susceptibility to proteolytic degradation, toxicity profile, and complexities in large-scale manufacture have hindered their development. To improve their proteolytic stability, methods such as integrating non-canonical amino acids (ncAAs) into their peptide sequence have been adopted, which also improves their potency and spectrum of action. The benefits of ncAA incorporation have been made possible by solid-phase peptide synthesis. However, this method is not always suitable for commercial production of AMPs because of poor yield, scale-up difficulties, and its non-'green' nature. Bioincorporation of ncAA as a method of integration is an emerging field geared towards tackling the challenges of solid-phase synthesis as a green, cheaper, and scalable alternative for commercialisation of AMPs. This review focusses on the bioincorporation of ncAAs; some challenges associated with the methods are outlined, and notes are given on how to overcome these challenges. The review focusses particularly on addressing two key challenges: AMP cytotoxicity towards microbial cell factories and the uptake of ncAAs that are unfavourable to them. Overcoming these challenges will draw us closer to a greater yield and an environmentally friendly and sustainable approach to make AMPs more druggable.
Topics: Amino Acids; Antimicrobial Peptides; Humans; Anti-Bacterial Agents; Solid-Phase Synthesis Techniques; Microbial Sensitivity Tests
PubMed: 38262069
DOI: 10.1002/psc.3560 -
Antibiotics (Basel, Switzerland) Dec 2023Mastitis, a highly prevalent disease in dairy cows, is responsible for massive financial losses due to decreased milk yield, milk quality, and costly medication. This...
Mastitis, a highly prevalent disease in dairy cows, is responsible for massive financial losses due to decreased milk yield, milk quality, and costly medication. This research paper investigates antimicrobial susceptibility in cows and the role played by both resistance and virulence gene distribution in bovine mastitis. A total of 984 raw milk samples were collected from five different dairy farms and cultured on sheep blood agar plates. Antimicrobial susceptibility was determined by disc diffusion, and corresponding resistance and virulence genes were detected by PCR. Among the collected milk samples, 73, 32, and 19 isolates of spp., spp., and coliforms were identified, respectively. The antimicrobial susceptibility results showed that spp. were resistant to tetracycline (86.30%), neomycin (79.45%), and oxacillin (73.97%). spp. were resistant to tetracycline (59.37%) and oxacillin (53.12%). Lastly, coliforms were resistant to oxacillin (100%) and bacitracin (68.42%). The genotyping results showed that spp. carried the resistance genes (46.57%) against tetracycline, (41.09%) against bacitracin, and (39.72%) against neomycin. spp. carried the resistance genes (40.62%) and (18.75%), and coliforms carried the resistance genes (42.10%) and (57.89%). Moreover, 57.53%, 75.0%, and 63.15% of spp., spp., and coliforms carried and virulence genes, respectively. All three tested bacterial genera showed no significant association between antimicrobial resistance genes and virulence factors, although they were negatively correlated ( > 0.05). The combination of resistance gene identification and susceptibility tests as components of the diagnosis of bovine mastitis can help in selecting effective antimicrobial agents to treat it.
PubMed: 38247595
DOI: 10.3390/antibiotics13010036