Multiple potential strategies for the application of nisin and derivatives.

Nisin is a naturally occurring bioactive small peptide produced by Lactococcus lactis subsp. lactis and belongs to the Type A (I) lantibiotics. Due to its potent antimicrobial activity, it has been broadly employed to preserve various food materials as well as to combat a variety of microbial pathogens. The present review discusses the antimicrobial properties of nisin and different types of their derivatives employed to treat microbial pathogens with a detailed underlying mechanism of action. Several alternative strategies such as combination, conjugation, and nanoformulations have been discussed in order to address several issues such as rapid degradation, instability, and reduced activity due to the various environmental factors that arise in the applications of nisin. Furthermore, the evolutionary relationship of many nisin genes from different nisin-producing bacterial species has been investigated. A detailed description of the natural and bioengineered nisin variants, as well as the underlying action mechanisms, has also been provided. The chemistry used to apply nisin in conjugation with natural or synthetic compounds as a synergetic mode of antimicrobial action has also been thoroughly discussed. The current review will be useful in learning about recent and past research that has been performed on nisin and its derivatives as antimicrobial agents.

Mixed biofilms of pathogenic Candida-bacteria: regulation mechanisms and treatment strategies.

Mixed-species biofilm is one of the most frequently recorded clinical problems. Mixed biofilms develop as a result of interactions between microorganisms of a single or multiple species (e.g. bacteria and fungi). Candida spp., particularly Candida albicans, are known to associate with various bacterial species to form a multi-species biofilm. Mixed biofilms of Candida spp. have been previously detected in vivo and on the surfaces of many biomedical instruments. Treating infectious diseases caused by mixed biofilms of Candida and bacterial species has been challenging due to their increased resistance to antimicrobial drugs. Here, we review and discuss the clinical significance of mixed Candida-bacteria biofilms as well as the signalling mechanisms involved in Candida-bacteria interactions. We also describe possible approaches for combating infections associated with mixed biofilms, such as the use of natural or synthetic drugs and combination therapy. The review presented here is expected to contribute to the advances in the biomedical field on the understanding of underlying interaction mechanisms of pathogens in mixed biofilm, and alternative approaches to treating the related infections.

Caffeine-loaded gold nanoparticles: antibiofilm and anti-persister activities against pathogenic bacteria.

The formation of biofilms by bacterial pathogens and the presence of persister cells in biofilms have become major concerns in the health sector, owing to their antibiotic resistance and tolerance. The transformation of bacterial pathogens into persister cells, either stochastically or due to stressful environmental factors, results in recalcitrant and recurring infections. Here, we sought to prepare gold nanoparticles from naturally occurring caffeine and explore their inhibitory action against biofilm formation and persister cells. Fourier transform infrared spectroscopy, UV-visible absorption spectroscopy, field emission transmission electron microscopy, energy-dispersive X-ray diffraction, and dynamic light scattering were used to characterize the gold nanoparticles obtained from caffeine (Caff-AuNPs). The Caff-AuNPs were found to exhibit a number of properties, including the ability to prevent biofilm formation, disperse mature biofilms, and kill different types of persister of gram-positive (Staphylococcus aureus and Listeria monocytogenes) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) pathogenic bacteria. Microscopic analysis of the aforementioned bacterial cells, treated with Caff-AuNPs, revealed the bactericidal effect of Caff-AuNPs, although the underlying mechanism remains unknown. Collectively, the Caff-AuNPs synthesized in this study may be used as potential drugs to combat chronic infections caused by biofilm-forming pathogenic bacteria. KEY POINTS: • Biofilm and persister cells are clinically relevant, as they either prolong or completely resist antibiotic treatments. • Caffeine is used in the green synthesis of Caff-AuNPs, which have antibacterial and antibiofilm properties. • Caff-AuNPs are effective against various pathogenic bacterial persister cells.

Suppression of hyphal formation and virulence of Candida albicans by natural and synthetic compounds.

Candida albicans undergoes a morphological yeast-to-hyphal transition during infection, which plays a significant role in its pathogenesis. The filamentous morphology of the hyphal form has been identified as a virulence factor as it facilitates surface adherence, intertwining with biofilm, invasion, and damage to host tissues and organs. Hence, inhibition of filamentation in addition to biofilm formation is considered a viable strategy against C. albicans infections. Furthermore, a good understanding of the signaling pathways involved in response to environmental cues driving hyphal growth is also critical to an understanding of C. albicans pathogenicity and to develop novel therapies. In this review, first the clinical significance and transcriptional control of C. albicans hyphal morphogenesis are addressed. Then, various strategies employed to suppress filamentation, prevent biofilm formation, and reduce virulence are discussed. These strategies include the inhibition of C. albicans filament formation using natural or synthetic compounds, and their combination with other agents or nanoformulations.

Combination Therapy for Bacterial Pathogens: Naturally Derived Antimicrobial Drugs Combined with Ulva lactuca Extract.

BACKGROUND: With the growing incidence of microbial pathogenesis, several alternative strategies have been developed. The number of treatments using naturally (e.g., plants, algae, fungi, bacteria, and animals) derived compounds has increased. Importantly, marine-derived products have become a promising and effective approach to combat the antibiotic resistance properties developed by bacterial pathogens. Furthermore, augmenting the sub-inhibitory concentration of the naturally-derived antimicrobial compounds (e.g., hydroxycinnamic acids, terpenes, marine-derived polysaccharides, phenolic compounds) into the naturally derived extracts as a combination therapy to treat the bacterial infection has not been well studied. OBJECTIVE: The present study was aimed to prepare green algae Ulva lactuca extract and evaluate its antibacterial activity towards Gram-positive and Gram-negative human pathogenic bacteria. Also, revitalize the antibacterial efficiency of the naturally-derived antimicrobial drugs and conventional antibiotics by mixing their sub-MIC to the U. lactuca extracts. METHODS: Extraction was done using a different organic solvent, and its antibacterial activity was tested towards Gram-positive and Gram-negative pathogens. The minimum inhibitory concentration (MIC) of U. lactuca extracts has been determined towards pathogenic bacteria using the micro broth dilution method. The viable cell counting method was used to determine the minimum bactericidal concentration (MBC). The fractional inhibitory concentration (FIC) assay was utilized to examine the combinatorial impact of sub-MIC of two antibacterial drugs using the micro broth dilution method. The chemical components of the extract were analyzed by GC-MS analysis. RESULTS: Among all the extracts, n-hexane extract was found to show effective antibacterial activity towards tested pathogens with the lowest MIC and MBC value. Furthermore, the n-hexane extracts have also been used to enhance the efficacy of the naturally-derived (derived from plants and marine organisms) compounds and conventional antibiotics at their sub-inhibitory concentrations. Most of the tested antibiotics and natural drugs at their sub-MIC were found to exhibit synergistic and additive antibacterial activity towards the tested bacterial pathogens. CONCLUSIONS: The combining of U. lactuca n-hexane extracts with natural drugs resulted in synergistic and additive bactericidal effects on Gram-positive and Gram-negative human pathogenic bacteria. The present study shows a new alternative strategy to revitalize the antimicrobial activity of naturally derived compounds for treating human bacterial pathogens.

Phloroglucinol and Its Derivatives: Antimicrobial Properties toward Microbial Pathogens.

Phloroglucinol (PG) is a natural product isolated from plants, algae, and microorganisms. Aside from that, the number of PG derivatives has expanded due to the discovery of their potential biological roles. Aside from its diverse biological activities, PG and its derivatives have been widely utilized to treat microbial infections caused by bacteria, fungus, and viruses. The rapid emergence of antimicrobial-resistant microbial infections necessitates the chemical synthesis of numerous PG derivatives in order to meet the growing demand for drugs. This review focuses on the use of PG and its derivatives to control microbial infection and the underlying mechanism of action. Furthermore, as future perspectives, some of the various alternative strategies, such as the use of PG and its derivatives in conjugation, nanoformulation, antibiotic combination, and encapsulation, have been thoroughly discussed. This review will enable the researcher to investigate the possible antibacterial properties of PG and its derivatives, either free or in the form of various formulations.

Inhibition of Virulence Factors and Biofilm Formation of Acinetobacter Baumannii by Naturally-derived and Synthetic Drugs.

Acinetobacter baumannii is a gram-negative, aerobic, non-motile, and pleomorphic bacillus. A. baumannii is also a highly-infectious pathogen causing high mortality and morbidity rates in intensive care units. The discovery of novel agents against A. baumannii infections is urgently needed due to the emergence of drug-resistant A. baumannii strains and the limited number of efficacious antibiotics available for treatment. In addition to the production of several virulence factors, A. baumannii forms biofilms on the host cell surface as well. Formation of biofilms occurs through initial surface attachment, microcolony formation, biofilm maturation, and detachment stages, and is one of the major drug resistance mechanisms employed by A. baumannii. Several studies have previously reported the efficacy of naturally-derived and synthetic compounds as anti- biofilm and anti-virulence agents against A. baumannii. Here, inhibition of biofilm formation and virulence factors of A. baumannii using naturally-derived and synthetic compounds are reviewed.

Caffeic Acid and Its Derivatives: Antimicrobial Drugs toward Microbial Pathogens.

Caffeic acid is a plant-derived compound that is classified as hydroxycinnamic acid which contains both phenolic and acrylic functional groups. Caffeic acid has been greatly employed as an alternative strategy to combat microbial pathogenesis and chronic infection induced by microbes such as bacteria, fungi, and viruses. Similarly, several derivatives of caffeic acid such as sugar esters, organic esters, glycosides, and amides have been chemically synthesized or naturally isolated as potential antimicrobial agents. To overcome the issue of water insolubility and poor stability, caffeic acid and its derivative have been utilized either in conjugation with other bioactive molecules or in nanoformulation. Besides, caffeic acid and its derivatives have also been applied in combination with antibiotics or photoirradiation to achieve a synergistic mode of action. The present review describes the antimicrobial roles of caffeic acid and its derivatives exploited either in free form or in combination or in nanoformulation to kill a diverse range of microbial pathogens along with their mode of action. The chemistry employed for the synthesis of the caffeic acid derivatives has been discussed in detail as well.