Listeria monocytogenes an Emerging Pathogen: a Comprehensive Overview on Listeriosis, Virulence Determinants, Detection, and Anti-Listerial Interventions.

Listeria monocytogenes, the third most deleterious zoonotic pathogen, is a major causative agent of animal and human listeriosis, an infection related to the consumption of contaminated food products. Even though, this pathogen has been responsible for the outbreaks of foodborne infections in the early 1980s, the major outbreaks have been reported during the past two decades. Listeriosis infection in the host is a rare but life-threatening disease with major public health and economic implications. Extensive reports on listeriosis outbreaks are associated with milk and milk products, meat and meat products, and fresh produce. This bacterium can adapt to any environmental and stress conditions, making it a prime causative agent for major foodborne diseases. The pathogen could survive an antibiotic treatment and persist in the host cell, thereby escaping the standard diagnostic practices. The current review strives to provide concise information on the epidemiology, serotypes, and pathogenesis of the L. monocytogenes to decipher the knowledge on the endurance of the pathogen inside the host and food products as a vehicle for Listeria contaminations. In addition, various detection methods for Listeria species from food samples and frontline regimens of L. monocytogenes treatment have also been discussed.

Deciphering the impact of Acinetobacter baumannii on human health, and exploration of natural compounds as efflux pump inhibitors to treat multidrug resistance.

Acinetobacter baumannii is an ESKAPE pathogen and threatens human health by generating infections with high fatality rates. A. baumannii leads to a spectrum of infections such as skin and wound infections, endocarditis, meningitis pneumonia, septicaemia and urinary tract infections. Recently, strains of A. baumannii have emerged as multidrug-resistant (MDR), meaning they are resistant to at least three different classes of antibiotics. MDR development is primarily intensified by widespread antibiotic misuse and inadequate stewardship. The World Health Organization (WHO) declared A. baumannii a precarious MDR species. A. baumannii maintains the MDR phenotype via a diverse array of antimicrobial metabolite-hydrolysing enzymes, efflux of antibiotics, impermeability and antibiotic target modification, thereby complicating treatment. Hence, a deeper understanding of the resistance mechanisms employed by MDR A. baumannii can give possible approaches to treat antimicrobial resistance. Resistance-nodulation-cell division (RND) efflux pumps have been identified as the key contributors to MDR determinants, owing to their capacity to force a broad spectrum of chemical substances out of the bacterial cell. Though synthetic inhibitors have been reported previously, their efficacy and safety are of debate. As resistance-modifying agents, phytochemicals are ideal choices. These natural compounds could eliminate the bacteria or interact with pathogenicity events and reduce the bacteria's ability to evolve resistance. This review aims to highlight the mechanism behind the multidrug resistance in A. baumannii and elucidate the utility of natural compounds as efflux pump inhibitors to deal with the infections caused by A. baumannii.

Fungal Infections as an Uprising Threat to Human Health: Chemosensitization of Fungal Pathogens With AFP From Aspergillus giganteus.

Occurrence and intensity of systemic invasive fungal infections have significantly risen in recent decades with large amount of mortality and morbidity rates at global level. Treatment therapy lies on the current antifungal interventions and are often limited due to the emergence of resistance to antifungal agents. Chemosensitization of fungal strains to the conventional antimycotic drugs are of growing concern. Current antifungal drugs often have been reported with poor activity and side effects to the host and have a few number of targets to manifest their efficacy on the pathogens. Indiscriminately, the aforementioned issues have been easily resolved by the development of new intervention strategies. One such approach is to employ combinational therapy that has exhibited a great level of inhibitions than that of a single compound. Chemosensitization of pathogenic mycoses to commercial antifungal drugs could be drastically enhanced by co-application of chemosensitizers along with the conventional drugs. Chemosensitizers could address the resistance mechanisms evolved in the pathogenic fungi and targeting the system to make the organism susceptible to commercially and clinically proven antifungal drugs. However, this strategy has not been overreached to the greater level, but it needs much attention to fight against not only with the pathogen but combat the resistance mechanisms of pathogens to drugs. Natural compounds including plant compounds and microbial proteins act as potential chemosensitizers to break the resistance in mycoses. Aspergillus giganteus, a filamentous fungus, is known to produce a cysteine rich extracellular protein called as antifungal protein (AFP). AFP has shown enhanced efficacy against several filamentous and non-filamentous fungal pathogens. On the basis of the reported studies on its targeted potential against pathogenic mycoses, AFP would be fabricated as a good chemosensitizer to augment the fungicidal efficacy of commercial antimycotic drugs. This paper reviews on breakthrough in the discovery of antifungal drugs along with the resistance patterns of mycoses to commercial drugs followed by the current intervention strategies applied to augment the fungicidal potential of drugs.

Pharmacokinetic profile of sarcin and thionin from Aspergillus giganteus and in vitro validation against human fungal pathogen.

Fungal infections are more predominant in agricultural and clinical fields. Aspergillosis caused by Aspergillus fumigatus leads to respiratory failure in patients along with various illnesses. Due to the limitation of antifungal therapy and antifungal drugs, there is an emergence to develop efficient antifungal compounds (AFCs) from natural sources to cure and prevent fungal infections. The present study deals with the investigation of the mechanism of the active compounds from Aspergillus giganteus against aspergillosis. Primarily, the bioavailability and toxicological properties of antifungal proteins such as, sarcin, thionin, chitinase and their derivatives have proved the efficiency of pharmacokinetic properties of selected compounds. Molecular interactions of selected compounds from A. giganteus with the virulence proteins of A. fumigatus (UDP-N-acetylglucosamine pyrophosphorylase, N-myristoyl transferase and Chitinase) have exhibited a good glide score and druggable nature of the AFCs. The antagonistic potential of AFCs on the pathogen was confirmed by SEM analysis where the shrunken and damaged spores of AFCs treated pathogen were observed. The integrity of A. fumigatus cell membrane and nuclear membrane treated with AFCs were analyzed by determining the release of cellular materials. The effective concentration of AFCs was found to be 250 µg/ml (P<0.0001). The GC-MS profiling has revealed the volatile bioactive metabolites present in A. giganteus. Further, interaction studies might provide more information on the synergism activity with the non-volatile metabolites which leads to the development of novel drugs for the treatment of aspergillosis.