Source Of Novel Antimicrobials Research Articles

Discovery and synthesis of leaderless bacteriocins from the Actinomycetota.

Leaderless bacteriocins are a unique class of bacteriocins that possess antimicrobial activity after translation and have few cases of documented resistance. Aureocin A53 and lacticin Q are considered two of the most well-studied leaderless bacteriocins. Here, we used in silico genome mining to search for novel aureocin A53-like leaderless bacteriocins in GenBank and MGnify. We identified 757 core peptides across 430 genomes with 75 species found currently without characterized leaderless bacteriocin production. These include putative novel species containing bacteriocin gene clusters (BGCs) from the genera Streptomyces (sp. NBC_00237) and Agrococcus (sp. SL85). To date, all characterized leaderless bacteriocins have been found within the phylum Bacillota, but this study identified 97 core peptides within the phylum Actinomycetota. Members of this phylum are traditionally associated with the production of antibiotics, such is the case with the genus Streptomyces. Actinomycetota is an underexplored phylum in terms of bacteriocin production with no characterized leaderless bacteriocin production to date. The two novel leaderless bacteriocins arcanocin and arachnicin from Actinomycetota members Arcanobacterium sp. and Arachnia sp., respectively, were chemically synthesized and antimicrobial activity was verified. These peptides were encoded in human gut (PRJNA485056) and oral (PRJEB43277) microbiomes, respectively. This research highlights the biosynthetic potential of Actinomycetota in terms of leaderless bacteriocin production and describes the first antimicrobial peptides encoded in the genera Arcanobacterium and Arachnia.IMPORTANCEBacteriocins are gathering attention as alternatives to current antibiotics given the increasing incidence of antimicrobial resistance. Leaderless bacteriocins are considered a commercially attractive subclass of bacteriocins due to the ability to synthesize active peptide and low levels of documented resistance. Therefore, in this work, we mined publicly available data to determine how widespread and diverse leaderless bacteriocins are within the domain of bacteria. Actinomycetota, known for its antibiotic producers but lacking described and characterized bacteriocins, proved to be a rich source of leaderless bacteriocins-97 in total. Two such peptides, arcanocin and arachnicin, were chemically synthesized and have antimicrobial activity. These bacteriocins may provide a novel source of novel antimicrobials that could aid in the development of future alternative antimicrobials and highlight that the Actinomycetota are an underexplored resource of bacteriocin peptides.

Genomic Exploration of a Chitinolytic Streptomyces albogriseolus PMB5 Strain from European mantis (Mantis religiosa).

The genus Streptomyces is renowned not only for its natural antibiotic production but also for its abundant chitinolytic enzymes, which break down stubborn chitin into chitooligosaccharides. Despite this, there have been limited studies utilizing whole-genome sequencing to explore the repertoire of chitin degradation and utilization genes in Streptomyces. A particularly compelling source of novel antimicrobials and enzymes lies in the microbiota of insects, where bacterial symbionts produce antimicrobials to protect against opportunistic pathogens and enzymes to adapt to the environment. In this study, we present the chitinolytic strain Streptomyces albogriseolus PMB5, isolated from the insectivorous Mantis religiosa (European mantis). Whole-genome sequencing revealed that PMB5 harbors a linear chromosome of 7,211,961 bp and a linear plasmid of 327,989 bp. The genome comprises 6683 genes, including 6592 protein-coding sequences and 91 RNA genes. Furthermore, genome analysis revealed 19 biosynthetic gene clusters covering polyketides, terpenes, and RiPPs, with 10 clusters showing significant gene similarity (>80%) to known clusters like antimycin, hopene, and geosmin. In the genome of S. albogriseolus PMB5, we were able to identify several antibiotic resistance genes; these included cml (resistance to phenicol), gimA (resistance to macrolides), parY (resistance to aminocoumarin), oleC/oleD (resistance to macrolides), novA (resistance to aminocoumarin) and bla/blc (resistance to beta-lactams). Additionally, three clusters displayed no similarity to known sequences, suggesting novel bioactive compound discovery potential. Remarkably, strain PMB5 is the first reported S. albogriseolus capable of thriving on a medium utilizing chitin as a carbon source, with over 50 chitin-utilizing genes identified, including five AA10 family LPMOs, five GH18 chitinases, and one GH19 chitinase. This study significantly enhances the genomic understanding of S. albogriseolus, a species previously underrepresented in research, paving the way to further exploration of the biotechnological potential of the species.

Elucidating the biotechnological potential of the genera Parageobacillus and Saccharococcus through comparative genomic and pan-genome analysis

BackgroundThe genus Geobacillus and its associated taxa have been the focal point of numerous thermophilic biotechnological investigations, both at the whole cell and enzyme level. By contrast, comparatively little research has been done on its recently delineated sister genus, Parageobacillus. Here we performed pan-genomic analyses on a subset of publicly available Parageobacillus and Saccharococcus genomes to elucidate their biotechnological potential.ResultsPhylogenomic analysis delineated the compared taxa into two distinct genera, Parageobacillus and Saccharococcus, with P. caldoxylosilyticus isolates clustering with S. thermophilus in the latter genus. Both genera present open pan-genomes, with the species P. toebii being characterized with the highest novel gene accrual. Diversification of the two genera is driven through the variable presence of plasmids, bacteriophages and transposable elements. Both genera present a range of potentially biotechnologically relevant features, including a source of novel antimicrobials, thermostable enzymes including DNA-active enzymes, carbohydrate active enzymes, proteases, lipases and carboxylesterases. Furthermore, they present a number of metabolic pathways pertinent to degradation of complex hydrocarbons and xenobiotics and for green energy production.ConclusionsComparative genomic analyses of Parageobacillus and Saccharococcus suggest that taxa in both of these genera can serve as a rich source of biotechnologically and industrially relevant secondary metabolites, thermostable enzymes and metabolic pathways that warrant further investigation.

A Mini-Review of Anti-Listerial Compounds from Marine Actinobacteria (1990-2023).

Among the foodborne illnesses, listeriosis has the third highest case mortality rate (20-30% or higher). Emerging drug-resistant strains of Listeria monocytogenes, a causative bacterium of listeriosis, exacerbate the seriousness of this public health concern. Novel anti-Listerial compounds are therefore needed to combat this challenge. In recent years, marine actinobacteria have come to be regarded as a promising source of novel antimicrobials. Hence, our aim was to provide a narrative of the available literature and discuss trends regarding bioprospecting marine actinobacteria for new anti-Listerial compounds. Four databases were searched for the review: Academic Search Ultimate, Google Scholar, ScienceDirect, and South African Thesis and Dissertations. The search was restricted to peer-reviewed full-text manuscripts that discussed marine actinobacteria as a source of antimicrobials and were written in English from 1990 to December 2023. In total, for the past three decades (1990-December 2023), only 23 compounds from marine actinobacteria have been tested for their anti-Listerial potential. Out of the 23 reported compounds, only 2-allyoxyphenol, adipostatins E-G, 4-bromophenol, and ansamycins (seco-geldanamycin B, 4.5-dihydro-17-O-demethylgeldanamycin, and seco-geldanamycin) have been found to possess anti-Listerial activity. Thus, our literature survey reveals the scarcity of published assays testing the anti-Listerial capacity of bioactive compounds sourced from marine actinobacteria during this period.

Antibacterial properties of secondary metabolites produced from wasp-associated bacteria in Isara, Remo-North, Ogun State, Nigeria

Background: Antibiotic resistance is a global problem with high morbidity and mortality in healthcare institution that requires an antimicrobial alternative and ittle is known of antibacterial agents derived from insect sources. Aim: The aim of the study was to examined antibacterial properties of secondary metabolites from insect-associated bacteria. Methods: Thirty-three wasps were obtained from abandoned structures in a local Community. Bacteria were isolated and identified by Sanger sequencing method. The metabolites were extracted and antibacterial potential was tested against different pathogens. The metabolites concentration was analyzed via High Performance Liquid Chromatography (HPLC). The metabolites and their clinical potentials were explored through STRING analysis. Results: Fifteen bacteria were isolated and 9 exhibited antibacterial properties consisting of Enterococcus faecalis (2). Pseudomonas fragi (2), Propionibacterium spp (1), Comamonas terrigena (2), Staphylococcus galinarum (1), Levi lactobacillus brevis (1). Antibiogram revealed that the secondary metabolite had inhibitory effects against all pathogens. The HPLC results indicated that the control and metabolites were eluted at 1.288 and 1.259 mins respectively with concentration ranging from 16.68 to 4761.82 mg/l. STRING analysis showed that the metabolites were gallidermin, enterocin, propionicin, and phenazine. Conclusion: The study concluded that the metabolites show activity against test strains and therefore a source of novel antimicrobials for addressing the global drug-resistant pathogens.

Antifungal properties of cathelicidin LL-37: current knowledge and future research directions.

The threat of fungal diseases is substantially underestimated worldwide, but they have serious consequences for humans, animals, and plants. Given the limited number of existing antifungal drugs together with the emergence of drug-resistant strains, many researchers have actively sought alternatives or adjuvants to antimycotics. The best way to tackle these issues is to unearth potential antifungal agents with new modes of action. Antimicrobial peptides are being hailed as a promising source of novel antimicrobials since they exhibit rapid and broad-spectrum microbicidal activities with a reduced likelihood of developing drug resistance. Recent years have witnessed an explosion in knowledge on microbicidal activity of LL-37, the sole human cathelicidin. Herein, we provide a summary of the current understanding about antifungal properties of LL-37, with particular emphasis on its molecular mechanisms. We further illustrate fruitful areas for future research. LL-37 is able to inhibit the growth of clinically and agronomically relevant fungi including Aspergillus, Candida, Colletotrichum, Fusarium, Malassezia, Pythium, and Trichophyton. Destruction of the cell wall integrity, membrane permeabilization, induction of oxidative stress, disruption of endoplasmic reticulum homeostasis, formation of autophagy-like structures, alterations in expression of numerous fungal genes, and inhibition of cell cycle progression are the key mechanisms underlying antifungal effects of LL-37. Burgeoning evidence also suggests that LL-37 may act as a potential anti-virulence peptide. It is hoped that this review will not only motivate researchers to conduct more detailed studies in this field, but also inspire further innovations in the design of LL-37-based drugs for the treatment of fungal infections.

Genomic and phenotypic characterization of Pseudomonas sp. GOM7, a novel marine bacterial species with antimicrobial activity against multidrug-resistant Staphylococcus aureus.

Antimicrobial resistance (AMR) represents a serious threat to global health. The development of new drugs to combat infections caused by bacteria resistant to multiple or even all available antibiotics is urgent. Most antibiotics used up to date have been identified from soil microorganisms. The marine environment represents an alternative source with great potential for the identification of microorganisms that produce bioactive molecules, including antibiotics. In this study, we analyzed the antibacterial activity of a collection of 82 bacterial strains isolated from marine water and sediment samples collected from the Southwestern Gulf of Mexico. Eight of the marine isolates inhibited the growth of different pathogenic bacteria, seven of which were identified as presumptive Pseudomonas aeruginosa. Interestingly, genome sequencing and phylogenetic analysis revealed that the remaining marine isolate showing antibacterial activity is a novel Pseudomonas species that we denominated Pseudomonas sp. GOM7, which was not pathogenic in the Galleria mellonella infection model in the conditions tested. Notably, Pseudomonas sp. GOM7 inhibited the growth of multidrug and methicillin-resistant strains of the priority pathogen Staphylococcus aureus. Our results show that the anti-S. aureus compound(s) produced by Pseudomonas sp. GOM7 can be extracted from the culture supernatant of this bacterium with the organic solvent ethyl acetate. Annotation of the Pseudomonas sp. GOM7 genome revealed the presence of several biosynthetic gene clusters predicted to code for possible antimicrobial compounds. Our results further highlight the potential of bacteria from the Gulf of Mexico as a source of novel antimicrobials.

Exploring Uncharted Marine Bacteria as a Source of Novel Antimicrobials

Marine microbes are defined by their habitat as microorganisms living in the sea or ocean. The term “marine microbes” includes viruses, protozoa and fungi. This microbial life constitutes 70% To 90% of marine biomass. More than 15000 bioactive compounds have been isolated from marine fungi, and other organisms and used as anti-inflammatory, and anticancer leads. Among the microorganisms of marine, bacteria are the least explored ones. Marine actinobacteria have adapted to high hydrostatic pressure, high concentration of Sodium Chloride, low concentration of organic matter, and low temperature. The phylum actinobacteria is a Gram-positive, nonmotile, and aerobic bacteria. Streptomyces and Actinomycetes are studied largely in this phylum due to their ability to produce a wide array of extracellular enzymes and secondary metabolites. Examples of active compounds isolated from Streptomyces include Fijimycins, etamycin A, Chlorinated bisindole pyrroles, and dynamics A–E. There may be diverse extremo enzymes hidden in the shadows that are currently unknown and, if discovered, may open up interesting new methods for the production and use of novel antimicrobials. In pharmaceutical research, a very small fraction of such organisms is studied. If discovered may open up interesting new ingenious, and cost-effective methods for the production and use of many novel anti-microbials.

Community and shotgun metagenomic analysis of Alligator mississippiensis oral cavity and GI tracts reveal complex ecosystems and potential reservoirs of antibiotic resistance

We report here the community structure and functional analysis of the microbiome of the Alligator mississippiensis GI tract from the oral cavity through the entirety of the digestive tract. Although many vertebrate microbiomes have been studied in recent years, the archosaur microbiome has only been given cursory attention. In the oral cavity we used amplicon-based community analysis to examine the structure of the oral microbiome during alligator development. We found a community that diversified over time and showed many of the hallmarks we would expect of a stable oral community. This is a bit surprising given the rapid turnover of alligator teeth but suggests that the stable gumline microbes are able to rapidly colonize the emerging teeth. As we move down the digestive tract, we were able to use both long and short read sequencing approaches to evaluate the community using a shotgun metagenomics approach. Long read sequencing was applied to samples from the stomach/duodenum, and the colorectal region, revealing a fairly uniform and low complexity community made up primarily of proteobacteria at the top of the gut and much more diversity in the colon. We used deep short read sequencing to further interrogate this colorectal community. The two sequencing approaches were concordant with respect to community structure but substantially more detail was available in the short read data, in spite of high levels of host DNA contamination. Using both approaches we were able to show that the colorectal community is a potential reservoir for antibiotic resistance, human pathogens such as Clostridiodes difficile and a possible source of novel antimicrobials or other useful secondary metabolites.

Evaluation of the Marine Bacterial Population in the Great Bitter Lake, Egypt, as a Source of Antimicrobial Secondary Metabolites

The ecological uniqueness of the Great Bitter Lake ecosystem makes its bacterial population interesting for investigation. Here, we present the first trial to evaluate the biosynthetic capacity of the bacterial population at the lake as a source of novel antimicrobials. We collected different samples from various locations throughout the lake including the oxic sediment, anoxic sediment, shore water, and off-shore water. We modified a molecular approach to compare and choose the samples with the highest bacterial biosynthetic capacity by quantifying the polyketide synthase gene clusters in their total community DNA. Furthermore, we screened the bacterial isolates recovered from these samples and their metabolic extracts for antimicrobial activity. We tried to tentatively investigate the identity of the active metabolites by PCR screening and LC–MS. The bacterial population in the oxic sediment had the highest biosynthetic capacity compared to other sample types. Four active Bacillus isolates were identified. The isolated Bacillus species were expected to produce numerous probable bioactive metabolites encoded by biosynthetic gene clusters related to the polyketide synthases (either individual or hybrid with non-ribosomal peptide synthetase), such as Bacillomycin D, Iturin A, Bacilosarcin B, Bacillcoumacin G and Macrolactin (N and G). These results suggest that the under-explored bacterial community of the Great Bitter Lake has a prospective biosynthetic capacity and can be a promising source for novel antibiotics.

Evaluating the Potential and Synergetic Effects of Microcins against Multidrug-Resistant Enterobacteriaceae.

ABSTRACTThe advent of multidrug-resistant bacteria has hampered the development of new antibiotics, exacerbating their morbidity and mortality. In this context, the gastrointestinal tract reveals a valuable source of novel antimicrobials. Microcins are bacteriocins produced by members of the family Enterobacteriaceae, which are endowed with a wide diversity of structures and mechanisms of action, and exert potent antibacterial activity against closely related bacteria. In this study, we investigated the antibacterial activities of four microcins against 54 Enterobacteriaceae isolates from three species (Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica). The selected microcins, microcin C (McC, nucleotide peptide), microcin J25 (MccJ25, lasso peptide), microcin B17 (MccB17, linear azol(in)e-containing peptide), and microcin E492 (MccE492, siderophore peptide) carry different post-translational modifications and have distinct mechanisms of action. MICs and minimal bactericidal concentrations (MBC) of the microcins were measured and the efficacy of combinations of the microcins together or with antibiotics was assessed to identify potential synergies. Every isolate showed sensitivity to at least one microcin with MIC values ranging between 0.02 μM and 42.5 μM. Among the microcins tested, McC exhibited the broadest spectrum of inhibition with 46 strains inhibited, closely followed by MccE492 with 38 strains inhibited, while MccJ25 showed the highest activity. In general, microcin activity was observed to be independent of antibiotic resistance profile and strain genus. Of the 42 tested combinations, 20 provided enhanced activity (18 out of 20 being microcin–antibiotic combinations), with two being synergetic.IMPORTANCE With their wide range of structures and mechanisms of action, microcins are shown to exert antibacterial activities against Enterobacteriaceae resistant to antibiotics together with synergies with antibiotics and in particular colistin.

Monomodular Pseudomonas aeruginosa phage JG004 lysozyme (Pae87) contains a bacterial surface-active antimicrobial peptide-like region and a possible substrate-binding subdomain.

Phage lysins are a source of novel antimicrobials to tackle the bacterial antibiotic-resistance crisis. The engineering of phage lysins is being explored as a game-changing technological strategy to introduce a more precise approach in the way in which antimicrobial therapy is applied. Such engineering efforts will benefit from a better understanding of lysin structure and function. In this work, the antimicrobial activity of the endolysin from Pseudomonas aeruginosa phage JG004, termed Pae87, has been characterized. This lysin had previously been identified as an antimicrobial agent candidate that is able to interact with the Gram-negative surface and disrupt it. Further evidence is provided here based on a structural and biochemical study. A high-resolution crystal structure of Pae87 complexed with a peptidoglycan fragment showed a separate substrate-binding region within the catalytic domain, 18 Å away from the catalytic site and located on the opposite side of the lysin molecule. This substrate-binding region was conserved among phylogenetically related lysins lacking an additional cell-wall-binding domain, but not among those containing such a module. Two glutamic acids were identified to be relevant for the peptidoglycan-degradation activity, although the antimicrobial activity of Pae87 was seemingly unrelated. Incontrast, an antimicrobial peptide-like region within the Pae87 C-terminus, named P87, was found to be able to actively disturb the outer membrane and display antibacterial activity by itself. Therefore, an antimicrobial mechanism for Pae87 is proposed in which the P87 peptide plays the role of binding to the outer membrane and disrupting the cell-wall function, either with or without the participation of the catalytic activity of Pae87.

Fighting antimicrobial resistance (AMR): Chinese herbal medicine as a source of novel antimicrobials - an update.

Antimicrobial resistance (AMR) has now emerged as a global public health crisis, requiring the discovery of new and novel antimicrobial compounds, that may be precursors of future therapeutic antibiotics. Chinese Herbal Medicine (CHM) comes with a rich pedigree of holistic and empirical usage in Asia for the last 5000years. Extracts of Anemarrhena asphodeloides Bunge, Angelica sinensis (Oliv.) Diels, Dianthus superbus L. Forsythiae fructus (Lian Qiao), Lonicerae flos (Jin Yin Hua), Naemorhedi cornu, Platycladus orientalis Franco, Polygonum aviculare, Polygonum cuspidatum, Poria cocos (Schw.), Rehmannia glutinosa (Gaertn.) DC, Rheum palmatum, Salvia miltiorrhiza Bunge, Scutellaria barbata, Scutellariae radix (Huang Qin) and Ursi fel (Xiong Dan) have shown to have antimicrobial properties against clinically significant Gram-negative and Gram-positive bacterial pathogens, as well as the mycobacteria (TB and non-tuberculous mycobacteria). Evidence is now beginning to emerge through systematic reviews of the outcomes of clinical studies employing CHM to treat infections. Of the 106 Cochrane systematic reviews on CHM, 16 (ca 15%) reviews examine CHM in the context of treating a specific infection disease or state. This update examines direct antimicrobial effect of CHM on bacterial pathogens, as well as synergistic effects of combining CHM with conventional antibiotics.

Antimicrobial activity of Rhipsalis baccifera and Drymoglossum piloselloides against Methicillin Resistant Staphylococcus Aureus and Drug Resistant Acinetobacter baumanii.

Methicillin Resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumanii are known to cause delayed healing of infections in both acute and chronic wounds. Plants are a natural source of novel antimicrobials and many new drugs are derived from plants, as plants contain phytochemicals that have antimicrobial activity. Sri Lanka is a tropical country with a wide variety of plant species, many of which were identified as possessing medicinal qualities and have been used by traditional medicinal practitioners in the treatment of various diseases and ailments. Dressings made of Rhipsalis baccifera and Drymoglossum piloselloides have been used to treat wounds by Sri Lankan traditional medicine practitioners. This study determined the antibacterial activity of aqueous and methanol extracts of R. baccifera and D. piloselloides against MRSA and Multidrug-resistant A. baumanii. Aqueous and methanolic extractions of both plants were done by maceration. Their antibacterial properties were checked against MRSA and A. baumanii by the well diffusion method. The effectiveness of the extract was further tested against factors like temperature and storage time. R. baccifera (aqueous extract) exhibited antimicrobial properties against MRSA but no activity against A. baumanii. The antibiotic activity against MRSA was increased after two months of storage at 4°C. D. piloselloides exhibited no antibiotic activity against both MRSA and A. baumanii. The methanolic extracts did not demonstrate any antibacterial activity.

Successful Development of Bacteriocins into Therapeutic Formulation for Treatment of MRSA Skin Infection in a Murine Model.

The emergence of antibiotic-resistant pathogens has caused a serious worldwide problem in infection treatment in recent years. One of the pathogens is methicillin-resistant Staphylococcus aureus (MRSA), which is a major cause of skin and soft tissue infections. Alternative strategies and novel sources of antimicrobials to solve antibiotic resistance problems are urgently needed. In this study, we explored the potential of two broad-spectrum bacteriocins, garvicin KS and micrococcin P1, in skin infection treatments. The two bacteriocins acted synergistically with each other and with penicillin G in killing MRSA in vitro The MICs of the antimicrobials in the three-component mixture were 40 ng/ml for micrococcin P1 and 2 μg/ml for garvicin KS and penicillin G, which were 62, 16, and at least 1,250 times lower than their MICs when assessed individually. To assess its therapeutic potential further, we challenged the three-component formulation in a murine skin infection model with the multidrug-resistant luciferase-tagged MRSA Xen31, a strain derived from the clinical isolate S. aureus ATCC 33591. Using the tagged-luciferase activity as a reporter for the presence of Xen31 in wounds, we demonstrated that the three-component formulation was efficient in eradicating the pathogen from treated wounds. Furthermore, compared to Fucidin cream, which is an antibiotic commonly used in skin infection treatments, our formulation was also superior in terms of preventing resistance development.

Bioprospecting the antimicrobial, antibiofilm and antiproliferative activity of Symplocos racemosa Roxb. Bark phytoconstituents along with their biosafety evaluation and detection of antimicrobial components by GC-MS

BackgroundPlants provide a ray of hope to combat the ever increasing antibiotic resistance and Symplocos racemosa is a valuable medicinal plant. The study focused on highlighting the importance of this plant’s phytoconstituents as potential source of novel antimicrobials against planktonic as well as biofilm forming microorganisms, along with their antiproliferative activity. The biosafety of the phytoconstituents was also established, followed by detection of probable antimicrobial components.MethodsThe best organic extractant and major groups of phytoconstituents were tested for their antimicrobial activity against reference microbial strains and drug-resistant clinical isolates. The anti-proliferative potential of the most active group of phytoconstituents was evaluated against cancerous cell lines. The in vitro biosafety of phytoconstituents was evaluated by Ames and MTT assay, while in vivo biosafety of the most active phytoconstituents, i.e., flavonoids was determined by acute oral toxicity. Further, the probable antimicrobial components in the flavonoids were detected by TLC and GC-MS.ResultsEthyl acetate extract was the most effective among various organic extracts, whereas phytoconstituents such as flavonoids, cardiac glycosides, saponins, tannins, triterpenes and phytosterols were the major groups present, with flavonoids being the most potent antimicrobials. The phytoconstituents displayed a significant antibiofilm potential, as exhibited by inhibition of initial cell attachment, disruption of the pre-formed biofilms and reduced metabolic activity of biofilms. The phytoconstituents were significantly active against the drug-resistant strains of E.coli, MRSA and Salmonella spp. Further, flavonoids showed significant cytotoxic effect against the cancerous cell lines but were non-cytotoxic against Vero (normal) cell line. All the test preparations were biosafe, as depicted by the Ames test and MTT assay. Also, flavonoids did not induce any abnormality in body weight, clinical signs, biochemical parameters and organs’ histopathology of the Swiss albino mice during in vivo acute oral toxicity studies. The flavonoids were resolved into 4 bands (S1-S4), where S3 was the most active and its GC-MS analysis revealed the presence of a number of compounds, where Bicyclo [2.2.1]heptan-2-one,1,7,7-trimethyl-, (1S)- was the most abundant.ConclusionsThese findings suggest that the phytoconstituents from Symplocos racemosa bark could act as potential source of antimicrobial as well as antiproliferative metabolites.

Actinobacteria Derived from Algerian Ecosystems as a Prominent Source of Antimicrobial Molecules.

Actinobacteria, in particular “rare actinobacteria” isolated from extreme ecosystems, remain the most inexhaustible source of novel antimicrobials, offering a chance to discover new bioactive metabolites. This is the first overview on actinobacteria isolated in Algeria since 2002 to date with the aim to present their potential in producing bioactive secondary metabolites. Twenty-nine new species and one novel genus have been isolated, mainly from the Saharan soil and palm groves, where 37.93% of the most abundant genera belong to Saccharothrix and Actinopolyspora. Several of these strains were found to produce antibiotics and antifungal metabolites, including 17 new molecules among the 50 structures reported, and some of these antibacterial metabolites have shown interesting antitumor activities. A series of approaches used to enhance the production of bioactive compounds is also presented as the manipulation of culture media by both classical methods and modeling designs through statistical strategies and the associations with diverse organisms and strains. Focusing on the Algerian natural sources of antimicrobial metabolites, this work is a representative example of the potential of a closely combined study on biology and chemistry of natural products.

Antarctic Streptomyces fildesensis So13.3 strain as a promising source for antimicrobials discovery

Antarctic have been suggested as an attractive source for antibiotics discovery and members of Streptomyces genus have historically been studied as natural producers of antimicrobial metabolites. Nonetheless, our knowledge on antibiotic-producing Streptomyces from Antarctic is very limited. In this study, the antimicrobial activity of organic extracts from Antarctic Streptomyces strains was evaluated by disk diffusion assays and minimum inhibitory concentration. The strain Streptomyces sp. So13.3 showed the greatest antibiotic activity (MIC = 15.6 μg/mL) against Gram-positive bacteria and growth reduction of Gram‒negative pathogens. The bioactive fraction in the crude extract was revealed by TLC‒bioautography at Rf = 0.78 with molecular weight between 148 and 624 m/z detected by LC-ESI-MS/MS. The strain So13.3 was taxonomically affiliated as Streptomyces fildesensis. Whole genome sequencing and analysis suggested a 9.47 Mb genome size with 42 predicted biosynthetic gene clusters (BGCs) and 56 putative clusters representing a 22% of total genome content. Interestingly, a large number of them (11 of 42 BGCs and 40 of 56 putative BGCs), did not show similarities with other known BGCs. Our results highlight the potential of the Antarctic Streptomyces strains as a promising source of novel antimicrobials, particularly the strain Streptomyces fildesensis So13.3, which first draft genome is reported in this work.

Antimicrobial properties of basidiomycota macrofungi to Mycobacterium abscessus isolated from patients with cystic fibrosis.

Antimicrobial resistance (AMR) has now emerged as a global public health crisis. Of particular concern is AMR associated with the genus Mycobacterium, including Mycobacterium tuberculosis and the nontuberculous mycobacteria (NTM). Emergence of the NTM, in particular Mycobacterium abscessus, in patients with cystic fibrosis (CF) represents both a diagnostic and a treatment dilemma. Such resistance drives the need to investigate novel sources of antimicrobials. Medicinal fungi have a well-documented history of use in traditional oriental therapies. Not only is this an ancient practice, but also still today, medical practice in Japan, China, Korea, and other Asian countries continue to rely on fungal-derived antibiotics. A study was, therefore, undertaken to examine the antimicrobial activity of 23 native macrofungal (mushrooms/toadstools) taxa, collected from woodlands in Northern Ireland against six clinical (CF) isolates of M. abscessus, as well as M. abscessus National Collection of Type Cultures (NCTC) Reference strain (NCTC 13031). Free-growing saprophytic and mycorrhizal macrofungi (n = 23) belonging to the phylum Basidiomycota were collected and were definitively identified employing Polymerase Chain reaction/ITS DNA sequencing. Macrofungal tissues were freeze-dried and reconstituted before employment in antibiotic susceptibility studies. All macrofungi examined showed varying inhibition of the M. abscessus isolates examined with the exception Russula nigricans. The macrofungi displaying maximum antimycobacterial activity against the clinical isolates were (in descending order) M. giganteus (33.6 mg/ml), Hygrocybe nigrescens (38.5 mg/ml) and Hypholoma fasciculare (25.3 mg/ml). Macrofungi may represent a source of novel antimicrobials against M. abscessus, which have not yet been fully explored nor exploited clinically. This is the first report describing the antimycobacterial properties of extracts of M. giganteus against M. abscessus. Further work is now required to identify the constituents and mode of the inhibitory action of these macrofungi against the M. abscessus. Given the gravity of AMR in the NTMs, particularly M. abscessus and the clinical treatment dilemmas that such AMR present, antibiotic drug discovery efforts should now focus on investigating and developing antibacterial compounds from macrofungi, particularly M. giganteus, where there are no or limited current treatment options.

Identification and classification of known and putative antimicrobial compounds produced by a wide variety of Bacillales species

BackgroundGram-positive bacteria of the Bacillales are important producers of antimicrobial compounds that might be utilized for medical, food or agricultural applications. Thanks to the wide availability of whole genome sequence data and the development of specific genome mining tools, novel antimicrobial compounds, either ribosomally- or non-ribosomally produced, of various Bacillales species can be predicted and classified. Here, we provide a classification scheme of known and putative antimicrobial compounds in the specific context of Bacillales species.ResultsWe identify and describe known and putative bacteriocins, non-ribosomally synthesized peptides (NRPs), polyketides (PKs) and other antimicrobials from 328 whole-genome sequenced strains of 57 species of Bacillales by using web based genome-mining prediction tools. We provide a classification scheme for these bacteriocins, update the findings of NRPs and PKs and investigate their characteristics and suitability for biocontrol by describing per class their genetic organization and structure. Moreover, we highlight the potential of several known and novel antimicrobials from various species of Bacillales.ConclusionsOur extended classification of antimicrobial compounds demonstrates that Bacillales provide a rich source of novel antimicrobials that can now readily be tapped experimentally, since many new gene clusters are identified.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3224-y) contains supplementary material, which is available to authorized users.