FabT, a Bacterial Transcriptional Repressor That Limits Futile Fatty Acid Biosynthesis.

Phospholipids are vital membrane constituents that determine cell functions and interactions with the environment. For bacterial pathogens, rapid adjustment of phospholipid composition to changing conditions during infection can be crucial for growth and survival. Fatty acid synthesis (FASII) regulators are central to this process. This review puts the spotlight on FabT, a MarR-family regulator of FASII characterized in streptococci, enterococci, and lactococci. Roles of FabT in virulence, as reported in mouse and nonhuman primate infection models, will be discussed. We present FabT structure, the FabT regulon, and changes in FabT regulation according to growth conditions. A unique feature of FabT concerns its modulation by an unconventional corepressor, acyl-acyl-carrier protein (ACP). Some bacteria express two ACP proteins, which are distinguished by their interactions with endogenous or exogenous fatty acid sources, one of which causes strong FabT repression. This system seems to allow preferred use of environmental fatty acids, thereby saving energy by limiting futile FASII activity. Control of fabT expression and FabT activity link various metabolic pathways to FASII. The various physiological consequences of FabT loss summarized here suggest that FabT has potential as a narrow range therapeutic target.

Bioactive Molecules of Mandarin Seed Oils Diminish Mycotoxin and the Existence of Fungi.

Mandarin is a favorite fruit of the citrus family. Mandarin seeds are considered a source of nontraditional oil obtained from byproduct materials. This investigation aimed to assess the biomolecules of mandarin seeds and evaluated their antimycotic and antimycotoxigenic impact on fungi. Moreover, it evaluated the protective role of mandarin oil against aflatoxin toxicity in cell lines. The two types of extracted oil (fixed and volatile) were ecofriendly. The fatty acid composition, tocopherol, sterols, and carotenoids were determined in the fixed oil, whereas volatiles and phenolics were estimated in the essential oil. A mixture of the two oils was prepared and evaluated for its antimicrobial impact. The reduction effect of this mixture was also investigated to reduce mycotoxin secretion using a simulated experiment. The protective effect of the oil was evaluated using healthy strains of cell lines. Fixed oil was distinguished by the omega fatty acid content (76.24%), lutein was the major carotenoid (504.3 mg/100 g) and it had a high ß-sitosterol content (294.6 mg/100 g). Essential oil contained limonene (66.05%), α-pinene (6.82%), ß-pinene (4.32%), and γ-terpinene (12.31%) in significant amounts, while gallic acid and catechol were recorded as the dominant phenolics. Evaluation of the oil mix for antimicrobial potency reflected a considerable impact against pathogenic bacteria and toxigenic fungi. By its application to the fungal media, this oil mix possessed a capacity for reducing mycotoxin secretion. The oil mix was also shown to have a low cytotoxic effect against healthy strains of cell lines and had potency in reducing the mortality impact of aflatoxin B1 applied to cell lines. These results recommend further study to involve this oil in food safety applications.

The reproductive tract microbiota in pregnancy.

The reproductive tract microbiota plays a crucial role in maintenance of normal pregnancy and influences reproductive outcomes. Microbe-host interactions in pregnancy remain poorly understood and their role in shaping immune modulation is still being uncovered. In this review, we describe the composition of vaginal microbial communities in the reproductive tract and their association with reproductive outcomes. We also consider strategies for manipulating microbiota composition by using live biotherapeutics, selective eradication of pathogenic bacteria with antibiotics and vaginal microbiota transplantation. Finally, future developments in this field and the need for mechanistic studies to explore the functional significance of reproductive tract microbial communities are highlighted.

Effects of Ulva sp. Extracts on the Growth, Biofilm Production, and Virulence of Skin Bacteria Microbiota: Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes Strains.

Ulva sp. is known to be a source of bioactive compounds such as ulvans, but to date, their biological activity on skin commensal and/or opportunistic pathogen bacteria has not been reported. In this study, the effects of poly- and oligosaccharide fractions produced by enzyme-assisted extraction and depolymerization were investigated, for the first time in vitro, on cutaneous bacteria: Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes. At 1000 µg/mL, poly- and oligosaccharide fractions did not affect the growth of the bacteria regarding their generation time. Polysaccharide Ulva sp. fractions at 1000 µg/mL did not alter the bacterial biofilm formation, while oligosaccharide fractions modified S. epidermidis and C. acnes biofilm structures. None of the fractions at 1000 µg/mL significantly modified the cytotoxic potential of S. epidermidis and S. aureus towards keratinocytes. However, poly- and oligosaccharide fractions at 1000 µg/mL induced a decrease in the inflammatory potential of both acneic and non-acneic C. acnes strains on keratinocytes of up to 39.8%; the strongest and most significant effect occurred when the bacteria were grown in the presence of polysaccharide fractions. Our research shows that poly- and oligosaccharide Ulva sp. fractions present notable biological activities on cutaneous bacteria, especially towards C. acnes acneic and non-acneic strains, which supports their potential use for dermo-cosmetic applications.

Inhibition of Three Potato Pathogens by Phenazine-Producing Pseudomonas spp. Is Associated with Multiple Biocontrol-Related Traits.

Phenazine-producing Pseudomonas spp. are effective biocontrol agents that aggressively colonize the rhizosphere and suppress numerous plant diseases. In this study, we compared the ability of 63 plant-beneficial phenazine-producing Pseudomonas strains representative of the worldwide diversity to inhibit the growth of three major potato pathogens: the oomycete Phytophthora infestans, the Gram-positive bacterium Streptomyces scabies, and the ascomycete Verticillium dahliae. The 63 Pseudomonas strains are distributed among four different subgroups within the P. fluorescens species complex and produce different phenazine compounds, namely, phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), 2-hydroxyphenazine-1-carboxylic acid, and 2-hydroxphenazine. Overall, the 63 strains exhibited contrasted levels of pathogen inhibition. Strains from the P. chlororaphis subgroup inhibited the growth of P. infestans more effectively than strains from the P. fluorescens subgroup. Higher inhibition was not associated with differential levels of phenazine production nor with specific phenazine compounds. The presence of additional biocontrol-related traits found in P. chlororaphis was instead associated with higher P. infestans inhibition. Inhibition of S. scabies by the 63 strains was more variable, with no clear taxonomic segregation pattern. Inhibition values did not correlate with phenazine production nor with specific phenazine compounds. No additional synergistic biocontrol-related traits were found. Against V. dahliae, PCN producers from the P. chlororaphis subgroup and PCA producers from the P. fluorescens subgroup exhibited greater inhibition. Additional biocontrol-related traits potentially involved in V. dahliae inhibition were identified. This study represents a first step toward harnessing the vast genomic diversity of phenazine-producing Pseudomonas spp. to achieve better biological control of potato pathogens. IMPORTANCE Plant-beneficial phenazine-producing Pseudomonas spp. are effective biocontrol agents, thanks to the broad-spectrum antibiotic activity of the phenazine antibiotics they produce. These bacteria have received considerable attention over the last 20 years, but most studies have focused only on the ability of a few genotypes to inhibit the growth of a limited number of plant pathogens. In this study, we investigated the ability of 63 phenazine-producing strains, isolated from a wide diversity of host plants on four continents, to inhibit the growth of three major potato pathogens: Phytophthora infestans, Streptomyces scabies, and Verticillium dahliae. We found that the 63 strains differentially inhibited the three potato pathogens. These differences are in part associated with the nature and the quantity of the phenazine compounds being produced but also with the presence of additional biocontrol-related traits. These results will facilitate the selection of versatile biocontrol agents against pathogens.

Recent Advances in Iron Chelation and Gallium-Based Therapies for Antibiotic Resistant Bacterial Infections.

Iron is essential for multiple bacterial processes and is thus required for host colonization and infection. The antimicrobial activity of multiple iron chelators and gallium-based therapies against different bacterial species has been characterized in preclinical studies. In this review, we provide a synthesis of studies characterizing the antimicrobial activity of the major classes of iron chelators (hydroxamates, aminocarboxylates and hydroxypyridinones) and gallium compounds. Special emphasis is placed on recent in-vitro and in-vivo studies with the novel iron chelator DIBI. Limitations associated with iron chelation and gallium-based therapies are presented, with emphasis on limitations of preclinical models, lack of understanding regarding mechanisms of action, and potential host toxicity. Collectively, these studies demonstrate potential for iron chelators and gallium to be used as antimicrobial agents, particularly in combination with existing antibiotics. Additional studies are needed in order to characterize the activity of these compounds under physiologic conditions and address potential limitations associated with their clinical use as antimicrobial agents.

The Hygiene Hypothesis - Learning From but Not Living in the Past.

Postulated by Strachan more than 30 years ago, the Hygiene Hypothesis has undergone many revisions and adaptations. This review journeys back to the beginnings of the Hygiene Hypothesis and describes the most important landmarks in its development considering the many aspects that have refined and generalized the Hygiene Hypothesis over time. From an epidemiological perspective, the Hygiene Hypothesis advanced to a comprehensive concept expanding beyond the initial focus on allergies. The Hygiene Hypothesis comprise immunological, microbiological and evolutionary aspects. Thus, the original postulate developed into a holistic model that explains the impact of post-modern life-style on humans, who initially evolved in close proximity to a more natural environment. Focusing on diet and the microbiome as the most prominent exogenous influences we describe these discrepancies and the resulting health outcomes and point to potential solutions to reestablish the immunological homeostasis that frequently have been lost in people living in developed societies.

Iron homeostasis in host and gut bacteria - a complex interrelationship.

Iron deficiency is the most frequent nutritional deficiency in the world with an estimated 1.4 billion people affected. The usual way to fight iron deficiency is iron fortification, but this approach is not always effective and can have undesirable side effects including an increase in the growth and virulence of gut bacterial pathogens responsible for diarrhea and gut inflammation. Iron is mainly absorbed in the duodenum and is tightly regulated in mammals. Unabsorbed iron enters the colonic lumen where many microorganisms, referred to as gut microbiota, reside. Iron is essential for these bacteria, and its availability consequently affects this microbial ecosystem. The aim of this review is to provide further insights into the complex relationship between iron and gut microbiota. Given that overcoming anemia caused by iron deficiency is still a challenge today, gut microbiota could help identify more efficient ways to tackle this public health problem.

Analysis of risk factors, pathogenic bacteria of maternal sepsis in term pregnant women with positive blood culture during hospitalization.

ABSTRACT: The objective of this study was to evaluate the risk factors, pathogenic bacteria and drug sensitivity of maternal sepsis, and provide evidence for clinical prevention and treatment.A retrospective investigation of pregnant women with full-term maternal sepsis was performed to analyze the risk factors, pathogenic bacteria, and drug sensitivity of maternal sepsis.Univariate analysis showed that temperature, serum procalcitonin (PCT) and C-reactive protein (CRP) at admission, white blood cell count (WBC), PCT, CRP and neutrophilic granulocyte percentage (N%) during fever, premature rupture of membranes (PROM), antibiotic use within 1 week, mode of production, onset and duration of fever, between groups were statistically significant (P < .05). Logistic regression analysis showed that cesarean section was an independent risk factor for sepsis (OR = 11.839, 95%CI: 3.121-44.906). Apparent increase was found in body temperature (OR = 3.664, 95%CI: 1.722-7.795), duration of fever (OR = 1.953, 95%CI: 1.242-3.071), and PCT (OR = 1.080, 95%CI: 1.002-1.163). Also, increasing neutrophil ratio (OR = 1.180, 95%CI: 1.073-1.297) indicated a high possibility of maternal sepsis. The organism Escherichia coli (E. coli) was the most common pathogenic bacteria in the positive blood culture group (90%), and the sensitivity to carbapenems (meropenem and imipenem/cilastatin) was 100%, that to piperacillin-tazobactam and amoxicillin sulbactam was over 90%, and that to ceftazidime was 95%.Cesarean section was an independent risk factor for maternal sepsis in term pregnant women with positive blood culture. Besides, the E. coli was the most common pathogenic bacteria in the positive blood culture group. Antibiotics should be used in time and reasonably when the temperature was significantly increased with elevated PCT and N% after a cesarean section.

Activity of Adesmia boronioides resinous exudate against phytopathogenic bacteria.

Resinous exudate obtained from the aerial parts of Adesmia boronioides Hook.f. were evaluated to determine anti-phytopathogenic effects. Briefly, resinous exudate was obtained by dipping fresh plant material in dichloromethane; chemical composition was determined by GC-MS; and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated against four phytopathogenic bacteria. Resinous exudate yield was 8.5% (resin/fresh plant), of which esquel-6-en-9-one (14.25%), esquel-7-en-9-one (5.86%), and veratric acid (2.59%) were the effective antibacterial compounds. Tested against Pectobacterium carotovorum subsp. carotovora, Erwinia amylovora, Bacillus subtilis, and Pseudomonas syringae, MICs and MBCs ranged from 16 to 128 µg/mL and 32-256 µg/mL, respectively. These results provide initial evidence that resinous bush A. boronioides is a new and alternative source of substances with agricultural interest.

Application of essential oils as antimicrobial agents against spoilage and pathogenic microorganisms in meat products.

Meat and meat products are perishable products that require the use additives to prevent the spoilage by foodborne microorganisms and pathogenic bacteria. Current trends for products without synthetic preservatives have led to the search for new sources of antimicrobial compounds. Essential oils (EOs), which has been used since ancient times, meet these goals since their effectiveness as antimicrobial agents in meat and meat products have been demonstrated. Cinnamon, clove, coriander, oregano, rosemary, sage, thyme, among others, have shown a greater potential to control and inhibit the growth of microorganisms. Although EOs are natural products, their quality must be evaluated before being used, allowing to grant the Generally Recognized as Safe (GRAS) classification. The bioactive compounds (BAC) present in their composition are linked to their activity, being the concentration and the quality of these compounds very important characteristics. Therefore, a single mechanism of action cannot be attributed to them. Extraction technique plays an important role, which has led to improve conventional techniques in favour of green emerging technologies that allow to preserve better target bioactive components, operating at lower temperatures and avoiding as much as possible the use of solvents, with more sustainable processing and reduced energy use and environmental pollution. Once extracted, these compounds display greater inhibition of gram-positive than gram-negative bacteria. Membrane disruption is the main mechanism of action involved. Their intense characteristics and the possible interaction with meat components make that their application combined with other EOs, encapsulated and being part of active film, increase their bioactivity without modifying the quality of the final product.

Marker assisted improvement of low soil phosphorus tolerance in the bacterial blight resistant, fine-grain type rice variety, Improved Samba Mahsuri.

Improved-Samba-Mahsuri (ISM), a high-yielding, popular bacterial blight resistant (possessing Xa21, xa13, and xa5), fine-grain type, low glycemic index rice variety is highly sensitive to low soil phosphorus (P). We have deployed marker-assisted backcross breeding (MABB) approach for targeted transfer of Pup1, a major QTL associated with low soil P tolerance, using Swarna as a donor. A new co-dominant marker, K20-1-1, which is specific for Pup1 was designed and used for foreground selection along with functional markers specific for the bacterial blight resistance genes, Xa21, xa13, and xa5. A set of 66 polymorphic SSR marker were used for the background selection along with a pair of flanking markers for the recombination selection in backcross derived progenies and in BC2F2 generation, 12 plants, which are homozygous for Pup1, all the three bacterial blight resistance genes and possessing agro-morphological traits equivalent to or better than ISM were selected and selfed to produce BC2F3s. They were evaluated in plots with low soil P and normal soil P at ICAR-IIRR, Hyderabad for their low soil P tolerance, and bacterial blight resistance and superior lines were advanced to BC2F6. One of the lines, when tested at multiple locations in India was found promising under both normal as well as low soil P conditions.

Bacterial Causes for Mortality Syndrome in Some Marine Fish Farms with Treatment Trials.

BACKGROUND AND OBJECTIVE: Bacterial fish diseases constitute a major problem in aquaculture, it was found in the environment and under stressors cause severe economic losses to fish. This work aimed to investigate the bacterial causes and suitable treatments of mass mortality in some cultured marine fish farms in Damietta governorate. MATERIALS AND METHODS: The study was performed on 5 farms suffered from mass mortality. Total of 100 diseased fish (10 sea bass and 10 sea bream/farm) and 20 water samples were randomly collected from these farms. Bacteriological examinations were carried out followed by in vitro sensitivity tests. Treatment trial was performed using the most effective antibacterial agent on isolated bacteria. RESULTS: From fish and water samples Pseudomonas spp., Aeromonas spp. and Vibrio spp. were isolated with the rat of (16, 10%), (22, 10%) and (28, 10%) respectively. These results were confirmed biochemically. Some virulence genes of isolated bacteria were detected using PCR; meanwhile, enrofloxacin reduced significantly the mortality rates in examined farms. CONCLUSION: It could be concluded that, Pseudomonas spp., Aeromonas spp. and Vibrio spp. are the main bacterial species causing mass mortality in marine fish farms. These bacteria were highly sensitive to enrofloxacin in vitro and in vivo.

Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment.

Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides.

Health-care systems that develop rapidly and efficiently may increase the lifespan of humans. Nevertheless, the older population is more fragile, and is at an increased risk of disease development. A concurrently growing number of surgeries and transplantations have caused antibiotics to be used much more frequently, and for much longer periods of time, which in turn increases microbial resistance. In 1945, Fleming warned against the abuse of antibiotics in his Nobel lecture: "The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant". After 70 years, we are witnessing the fulfilment of Fleming's prophecy, as more than 700,000 people die each year due to drug-resistant diseases. Naturally occurring antimicrobial peptides protect all living matter against bacteria, and now different peptidomimetic strategies to engineer innovative antibiotics are being developed to defend humans against bacterial infections.

Magnetite Nanoparticles and Essential Oils Systems for Advanced Antibacterial Therapies.

Essential oils (EOs) have attracted considerable interest in the past few years, with increasing evidence of their antibacterial, antiviral, antifungal, and insecticidal effects. However, as they are highly volatile, the administration of EOs to achieve the desired effects is challenging. Therefore, nanotechnology-based strategies for developing nanoscaled carriers for their efficient delivery might offer potential solutions. Owing to their biocompatibility, biodegradability, low toxicity, ability to target a tissue specifically, and primary structures that allow for the attachment of various therapeutics, magnetite nanoparticles (MNPs) are an example of such nanocarriers that could be used for the efficient delivery of EOs for antimicrobial therapies. The aim of this paper is to provide an overview of the use of EOs as antibacterial agents when coupled with magnetite nanoparticles (NPs), emphasizing the synthesis, properties and functionalization of such NPs to enhance their efficiency. In this manner, systems comprising EOs and MNPs could offer potential solutions that could overcome the challenges associated with biofilm formation on prosthetic devices and antibiotic-resistant bacteria by ensuring a controlled and sustained release of the antibacterial agents.

New Agents in Development for Sepsis: Any Reason for Hope?

Sepsis is a syndrome which is defined as a dysregulated host response to infection leading to organ failure. Since it remains one of the leading causes of mortality worldwide, numerous drug candidates have already been tested, and continue to be developed, as potential adjunct therapies. Despite convincing mechanisms of action and robust pre-clinical data, almost all drug candidates in the field of sepsis have failed to demonstrate clinical efficacy in the past two decades. Accordingly, the development of new sepsis drugs has markedly decreased in the past few years. Nevertheless, thanks to a better understanding of sepsis pathophysiology and pathways, new promising drug candidates are currently being developed. Instead of a unique sepsis profile as initially suspected, various phenotypes have been characterised. This has  resulted in the identification of multiple targets for new drugs together with relevant biomarkers, and a better understanding of the most appropriate time to intervention. Within the entire sepsis drugs portfolio, those targeting the immune response are probably the most promising. Monoclonal antibodies targeting either cytokines or infectious agents are undoubtedly part of the potential successful therapeutic classes to come.

Assessment of the antibacterial, antivirulence, and action mechanism of Copaifera pubiflora oleoresin and isolated compounds against oral bacteria.

The microorganisms that constitute the oral microbiome can cause oral diseases, including dental caries and endodontic infections. The use of natural products could help to overcome bacterial resistance to the antimicrobials that are currently employed in clinical therapy. This study assessed the antimicrobial activity of the Copaifera pubiflora oleoresin and of the compounds isolated from this resin against oral bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays provided values ranging from 6.25 to > 400 µg/mL for the C. pubiflora oleoresin and its isolated compounds. The fractional inhibitory concentration index (FICI) assay showed that the oleoresin and chlorhexidine did not act synergistically. All the tested bacterial strains formed biofilms. MICB50 determination revealed inhibitory action: values varied from 3.12-25 µg/mL for the oleoresin, and from 0.78 to 25 µg/mL for the ent-hardwickiic acid. Concerning biofilm eradication, the C. pubiflora oleoresin and hardwickiic acid eradicated 99.9 % of some bacterial biofilms. Acid resistance determination showed that S. mutans was resistant to acid in the presence of the oleoresin and ent-hardwickiic acid at pH 4.0, 4.5, and 5.0 at all the tested concentrations. Analysis of DNA/RNA and protein release by the cell membrane demonstrated that the oleoresin and hardwiickic acid damaged the bacterial membrane irreversibly, which affected membrane integrity. Therefore, the C. pubiflora oleoresin and ent-hardwickiic acid have potential antibacterial effect and can be used as new therapeutic alternatives to treat oral diseases such as dental caries and endodontic infections.

Bacteria as a double-action sword in cancer.

Bacteria have long been known as one of the primary causative agents of cancer, however, recent studies suggest that they can be used as a promising agent in cancer therapy. Because of the limitations that conventional treatment faces due to the specific pathophysiology and the tumor environment, there is a great need for the new anticancer therapeutic agents. Bacteriotherapy utilizes live, attenuated strains or toxins, peptides, bacteriocins of the bacteria in the treatment of cancer. Moreover, they are widely used as a vector for delivering genes, peptides, or drugs to the tumor target. Interestingly, it was found that their combination with the conventional therapeutic approaches may enhance the treatment outcome. In the genome editing era, it is feasible to develop a novel generation of therapeutic bacteria with fewer side effects and more efficacy for cancer therapy. Here we review the current knowledge on the dual role of bacteria in the development of cancer as well as cancer therapy.