Showing papers on "Bacteria published in 2023"

Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies

Abstract: Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.

Ubiquitin-like conjugation by bacterial cGAS enhances anti-phage defence

Abstract: cGAS is an evolutionarily conserved enzyme that has a pivotal role in immune defence against infection1-3. In vertebrate animals, cGAS is activated by DNA to produce cyclic GMP-AMP (cGAMP)4,5, which leads to the expression of antimicrobial genes6,7. In bacteria, cyclic dinucleotide (CDN)-based anti-phage signalling systems (CBASS) have been discovered8-11. These systems are composed of cGAS-like enzymes and various effector proteins that kill bacteria on phage infection, thereby stopping phage spread. Of the CBASS systems reported, approximately 39% contain Cap2 and Cap3, which encode proteins with homology to ubiquitin conjugating (E1/E2) and deconjugating enzymes, respectively8,12. Although these proteins are required to prevent infection of some bacteriophages8, the mechanism by which the enzymatic activities exert an anti-phage effect is unknown. Here we show that Cap2 forms a thioester bond with the C-terminal glycine of cGAS and promotes conjugation of cGAS to target proteins in a process that resembles ubiquitin conjugation. The covalent conjugation of cGAS increases the production of cGAMP. Using a genetic screen, we found that the phage protein Vs.4 antagonized cGAS signalling by binding tightly to cGAMP (dissociation constant of approximately 30 nM) and sequestering it. A crystal structure of Vs.4 bound to cGAMP showed that Vs.4 formed a hexamer that was bound to three molecules of cGAMP. These results reveal a ubiquitin-like conjugation mechanism that regulates cGAS activity in bacteria and illustrates an arms race between bacteria and viruses through controlling CDN levels.

Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria

Abstract: Antimicrobial resistance (AMR) has become a major problem in public health leading to an estimated 4.95 million deaths in 2019. The selective pressure caused by the massive and repeated use of antibiotics has led to bacterial strains that are partially or even entirely resistant to known antibiotics. AMR is caused by several mechanisms, among which the (over)expression of multidrug efflux pumps plays a central role. Multidrug efflux pumps are transmembrane transporters, naturally expressed by Gram-negative bacteria, able to extrude and confer resistance to several classes of antibiotics. Targeting them would be an effective way to revive various options for treatment. Many efflux pump inhibitors (EPIs) have been described in the literature; however, none of them have entered clinical trials to date. This review presents eight families of EPIs active against Escherichia coli or Pseudomonas aeruginosa. Structure–activity relationships, chemical synthesis, in vitro and in vivo activities, and pharmacological properties are reported. Their binding sites and their mechanisms of action are also analyzed comparatively.

Horizontal Gene Transfer of Antibiotic Resistance Genes in Biofilms

Abstract: Most bacteria attach to biotic or abiotic surfaces and are embedded in a complex matrix which is known as biofilm. Biofilm formation is especially worrisome in clinical settings as it hinders the treatment of infections with antibiotics due to the facilitated acquisition of antibiotic resistance genes (ARGs). Environmental settings are now considered as pivotal for driving biofilm formation, biofilm-mediated antibiotic resistance development and dissemination. Several studies have demonstrated that environmental biofilms can be hotspots for the dissemination of ARGs. These genes can be encoded on mobile genetic elements (MGEs) such as conjugative and mobilizable plasmids or integrative and conjugative elements (ICEs). ARGs can be rapidly transferred through horizontal gene transfer (HGT) which has been shown to occur more frequently in biofilms than in planktonic cultures. Biofilm models are promising tools to mimic natural biofilms to study the dissemination of ARGs via HGT. This review summarizes the state-of-the-art of biofilm studies and the techniques that visualize the three main HGT mechanisms in biofilms: transformation, transduction, and conjugation.

Antimicrobial Exposures in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation

Abstract: Rationale: Data suggest that altered antimicrobial concentrations are likely during extracorporeal membrane oxygenation (ECMO). Objectives: The primary aim of this analysis was to describe the pharmacokinetics (PKs) of antimicrobials in critically ill adult patients receiving ECMO. Our secondary aim was to determine whether current antimicrobial dosing regimens achieve effective and safe exposure. Methods: This study was a prospective, open-labeled, PK study in six ICUs in Australia, New Zealand, South Korea, and Switzerland. Serial blood samples were collected over a single dosing interval during ECMO for 11 antimicrobials. PK parameters were estimated using noncompartmental methods. Adequacy of antimicrobial dosing regimens were evaluated using predefined concentration exposures associated with maximal clinical outcomes and minimal toxicity risks. Measurements and Main Results: We included 993 blood samples from 85 patients. The mean age was 44.7 ± 14.4 years, and 61.2% were male. Thirty-eight patients (44.7%) were receiving renal replacement therapy during the first PK sampling. Large variations (coefficient of variation of ⩾30%) in antimicrobial concentrations were seen leading to more than fivefold variations in all PK parameters across all study antimicrobials. Overall, 70 (56.5%) concentration profiles achieved the predefined target concentration and exposure range. Target attainment rates were not significantly different between modes of ECMO and renal replacement therapy. Poor target attainment was observed across the most frequently used antimicrobials for ECMO recipients, including for oseltamivir (33.3%), piperacillin (44.4%), and vancomycin (27.3%). Conclusions: Antimicrobial PKs were highly variable in critically ill patients receiving ECMO, leading to poor target attainment rates. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000559819).

Microalgae-Derived Pigments for the Food Industry

Abstract: In the food industry, manufacturers and customers have paid more attention to natural pigments instead of the synthetic counterparts for their excellent coloring ability and healthy properties. Microalgae are proven as one of the major photosynthesizers of naturally derived commercial pigments, gaining higher value in the global food pigment market. Microalgae-derived pigments, especially chlorophylls, carotenoids and phycobiliproteins, have unique colors and molecular structures, respectively, and show different physiological activities and health effects in the human body. This review provides recent updates on characteristics, application fields, stability in production and extraction processes of chlorophylls, carotenoids and phycobiliproteins to standardize and analyze their commercial production from microalgae. Potential food commodities for the pigment as eco-friendly colorants, nutraceuticals, and antioxidants are summarized for the target products. Then, recent cultivation strategies, metabolic and genomic designs are presented for high pigment productivity. Technical bottlenecks of downstream processing are discussed for improved stability and bioaccessibility during production. The production strategies of microalgal pigments have been exploited to varying degrees, with some already being applied at scale while others remain at the laboratory level. Finally, some factors affecting their global market value and future prospects are proposed. The microalgae-derived pigments have great potential in the food industry due to their high nutritional value and competitive production cost.

Profiling the human intestinal environment under physiological conditions

Abstract: Abstract The spatiotemporal structure of the human microbiome 1,2 , proteome 3 and metabolome 4,5 reflects and determines regional intestinal physiology and may have implications for disease 6 . Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals 7 . To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

An Update on Eukaryotic Viruses Revived from Ancient Permafrost

Abstract: One quarter of the Northern hemisphere is underlain by permanently frozen ground, referred to as permafrost. Due to climate warming, irreversibly thawing permafrost is releasing organic matter frozen for up to a million years, most of which decomposes into carbon dioxide and methane, further enhancing the greenhouse effect. Part of this organic matter also consists of revived cellular microbes (prokaryotes, unicellular eukaryotes) as well as viruses that remained dormant since prehistorical times. While the literature abounds on descriptions of the rich and diverse prokaryotic microbiomes found in permafrost, no additional report about “live” viruses have been published since the two original studies describing pithovirus (in 2014) and mollivirus (in 2015). This wrongly suggests that such occurrences are rare and that “zombie viruses” are not a public health threat. To restore an appreciation closer to reality, we report the preliminary characterizations of 13 new viruses isolated from 7 different ancient Siberian permafrost samples, 1 from the Lena river and 1 from Kamchatka cryosol. As expected from the host specificity imposed by our protocol, these viruses belong to 5 different clades infecting Acanthamoeba spp. but not previously revived from permafrost: Pandoravirus, Cedratvirus, Megavirus, and Pacmanvirus, in addition to a new Pithovirus strain.

Trends in Pseudomonas aeruginosa (P. aeruginosa) Bacteremia during the COVID-19 Pandemic: A Systematic Review

Abstract: Pseudomonas aeruginosa (P. aeruginosa) is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in cases of P. aeruginosa bacteremia. It remains unclear how the incidence of P. aeruginosa bacteremia changed during the Coronavirus Disease 2019 (COVID-19) pandemic, with studies showing almost contradictory conclusions despite enhanced infection control practices during the pandemic. This systematic review sought to examine published reports with incidence rates for P. aeruginosa bacteremia during (defined as from March 2020 onwards) and prior to the COVID-19 pandemic. A systematic literature search was conducted in accordance with PRISMA guidelines and performed in Cochrane, Embase, and Medline with combinations of the key words (pseudomonas aeruginosa OR PAE) AND (incidence OR surveillance), from database inception until 1 December 2022. Based on the pre-defined inclusion criteria, a total of eight studies were eligible for review. Prior to the pandemic, the prevalence of P. aeruginosa was on an uptrend. Several international reports found a slight increase in the incidence of P. aeruginosa bacteremia during the COVID-19 pandemic. These findings collectively highlight the continued importance of good infection prevention and control and antimicrobial stewardship during both pandemic and non-pandemic periods. It is important to implement effective infection prevention and control measures, including ensuring hand hygiene, stepping up environmental cleaning and disinfection efforts, and developing timely guidelines on the appropriate prescription of antibiotics.

Genomically mined acoustic reporter genes for real-time in vivo monitoring of tumors and tumor-homing bacteria

Abstract: Abstract Ultrasound allows imaging at a much greater depth than optical methods, but existing genetically encoded acoustic reporters for in vivo cellular imaging have been limited by poor sensitivity, specificity and in vivo expression. Here we describe two acoustic reporter genes (ARGs)—one for use in bacteria and one for use in mammalian cells—identified through a phylogenetic screen of candidate gas vesicle gene clusters from diverse bacteria and archaea that provide stronger ultrasound contrast, produce non-linear signals distinguishable from background tissue and have stable long-term expression. Compared to their first-generation counterparts, these improved bacterial and mammalian ARGs produce 9-fold and 38-fold stronger non-linear contrast, respectively. Using these new ARGs, we non-invasively imaged in situ tumor colonization and gene expression in tumor-homing therapeutic bacteria, tracked the progression of tumor gene expression and growth in a mouse model of breast cancer, and performed gene-expression-guided needle biopsies of a genetically mosaic tumor, demonstrating non-invasive access to dynamic biological processes at centimeter depth.

Clinical applications of antimicrobial photodynamic therapy in dentistry

Abstract: Given the emergence of resistant bacterial strains and novel microorganisms that globally threaten human life, moving toward new treatment modalities for microbial infections has become a priority more than ever. Antimicrobial photodynamic therapy (aPDT) has been introduced as a promising and non-invasive local and adjuvant treatment in several oral infectious diseases. Its efficacy for elimination of bacterial, fungal, and viral infections and key pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Candida albicans, and Enterococcus faecalis have been investigated by many invitro and clinical studies. Researchers have also investigated methods of increasing the efficacy of such treatment modalities by amazing developments in the production of natural, nano based, and targeted photosensitizers. As clinical studies have an important role in paving the way towards evidence-based applications in oral infection treatment by this method, the current review aimed to provide an overall view of potential clinical applications in this field and summarize the data of available randomized controlled clinical studies conducted on the applications of aPDT in dentistry and investigate its future horizons in the dental practice. Four databases including PubMed (Medline), Web of Science, Scopus and Embase were searched up to September 2022 to retrieve related clinical studies. There are several clinical studies reporting aPDT as an effective adjunctive treatment modality capable of reducing pathogenic bacterial loads in periodontal and peri-implant, and persistent endodontic infections. Clinical evidence also reveals a therapeutic potential for aPDT in prevention and reduction of cariogenic organisms and treatment of infections with fungal or viral origins, however, the number of randomized clinical studies in these groups are much less. Altogether, various photosensitizers have been used and it is still not possible to recommend specific irradiation parameters due to heterogenicity among studies. Reaching effective clinical protocols and parameters of this treatment is difficult and requires further high quality randomized controlled trials focusing on specific PS and irradiation parameters that have shown to have clinical efficacy and are able to reduce pathogenic bacterial loads with sufficient follow-up periods.

Alginate and derivatives hydrogels in encapsulation of probiotic bacteria: An updated review

Abstract: Natural hydrogels such as alginate are hopeful gadgets for cellular encapsulation, drug delivery, and many others because of their properties, such as biodegradable and non-toxic for the environment. Probiotics, as intestinal microbiota, have numerous benefits for the host's health. On the other hand, the survival of probiotics is critical, especially in the food and medicine industry, and probiotics should endure disagreeable status that occurs in passing through the gastrointestinal system. Encapsulation can be applied to protect probiotics but increase their bio-accessibility, so the survival rate of bacteria and their transportation to different body parts. In this review, the literature on delivery systems results focuses on combining alginates with other biopolymers to produce hydrogels that enclose probiotics, only increasing their encapsulation performance and survival compared to alginates in gastrointestinal simulation conditions collected. All the tastes and limitations, along with the benefits of microencapsulation of probiotics using hydrogels, can lead to the emergence of biopolymers, new ways of protecting probiotics, and ultimately producing products that are safe for consumers.

L-form conversion in Gram-positive bacteria enables escape from phage infection

Abstract: Abstract At the end of a lytic bacteriophage replication cycle in Gram-positive bacteria, peptidoglycan-degrading endolysins that cause explosive cell lysis of the host can also attack non-infected bystander cells. Here we show that in osmotically stabilized environments, Listeria monocytogenes can evade phage predation by transient conversion to a cell wall-deficient L-form state. This L-form escape is triggered by endolysins disintegrating the cell wall from without, leading to turgor-driven extrusion of wall-deficient, yet viable L-form cells. Remarkably, in the absence of phage predation, we show that L-forms can quickly revert to the walled state. These findings suggest that L-form conversion represents a population-level persistence mechanism to evade complete eradication by phage attack. Importantly, we also demonstrate phage-mediated L-form switching of the urinary tract pathogen Enterococcus faecalis in human urine, which underscores that this escape route may be widespread and has important implications for phage- and endolysin-based therapeutic interventions.

Simultaneous Detection of L-Lactate and D-Glucose Using DNA Aptamers in Human Blood Serum.

Abstract: L-lactate is a key metabolite indicative of physiological states, glycolysis pathways, and various diseases such as sepsis, heart attack, lactate acidosis, and cancer. Detection of lactate has been relying on a few enzymes that need other substrates. In this work, DNA aptamers for L-lactate were obtained using a library-immobilization selection method and the highest affinity aptamer reached a Kd of 0.43 mM as determined using isothermal titration calorimetry. The aptamers showed up to 50-fold selectivity for L-lactate over D-lactate and had little responses to other closely related analogs such as pyruvate and 3-hydroxybutyrate. A fluorescent biosensor based on the strand displacement method showed a limit of detection of 0.55 mM L-lactate, and the sensor worked in 90% serum. Simultaneous detection of L-lactate and D-glucose in the same solution was achieved. This work has broadened the scope of aptamers to simple metabolites and provided a useful probe for continuous and multiplexed monitoring.

Antimicrobial Hybrid Amphiphile via Dynamic Covalent Bonds Enables Bacterial Biofilm Dispersal and Bacteria Eradication

Abstract: To tackle the problems caused by bacterial biofilms, herein, this study reports an antimicrobial hybrid amphiphile (aHA) via dynamic covalent bonds for eradicating staphylococcal biofilms. aHA is synthesized via iminoboronate ester formation between DETA NONOate (nitric oxide donor), 3 4‐dihydroxybenaldehyde, and phenylboronic acid‐modified ciprofloxacin (Cip). aHA can self‐assemble in aqueous solution with an ultra‐small critical aggregation concentration of 3.80 × 10–5 mm and high drug loading content of 73.8%. The iminoboronate ester is sensitive to the acidic and oxidative biofilm microenvironment, liberating nitric oxide and Cip that can synergistically eradicate bacterial biofilms. To this end, aHA assemblies efficiently eradicate staphylococcal infections and ameliorate inflammation in the murine peritoneal and subcutaneous infection models without any notable side effects on normal tissues. Collectively, the aHA assemblies may provide a facile and efficient alternative to the current development of anti‐biofilm therapies.

Molecular ecological networks reveal the spatial-temporal variation of microbial communities in drinking water distribution systems.

Abstract: Microbial activity and regrowth in drinking water distribution systems is a major concern for water service companies. However, previous studies have focused on the microbial composition and diversity of the drinking water distribution systems (DWDSs), with little discussion on microbial molecular ecological networks (MENs) in different water supply networks. MEN analysis explores the potential microbial interaction and the impact of environmental stress, to explain the characteristics of microbial community structures. In this study, the random matrix theory-based network analysis was employed to investigate the impact of seasonal variation including water source switching on the networks of three DWDSs that used different disinfection methods. The results showed that microbial interaction varied slightly with the seasons but was significantly influenced by different DWDSs. Proteobacteria, identified as key species, play an important role in the network. Combined UV-chlorine disinfection can effectively reduce the size and complexity of the network compared to chlorine disinfection alone, ignoring seasonal variations, which may affect microbial activity or control microbial regrowth in DWDSs. This study provides new insights for analyzing the dynamics of microbial interactions in DWDSs.

Single Copper Atom Photocatalyst Powers an Integrated Catalytic Cascade for Drug-Resistant Bacteria Elimination.

Abstract: To address the issue posed by drug-resistant bacteria and inspired by natural antimicrobial enzymes, we report the atomically doped copper on guanine-derived nanosheets (G-Cu) that possess the integrated catalytic cascade property of glucose oxidase and peroxidase, yielding free radicals to eliminate drug-resistant bacteria upon light irradiation. Density functional theory calculations demonstrate that copper could notably promote oxygen activation and H2O2 splitting on the G-Cu complexes. Further all-atom simulation and experimental data indicate that the lysis of bacteria is mainly induced by cell membrane damage and the elevation of intracellular reactive oxygen species. Lastly, the G-Cu complexes efficiently eliminate the staphylococci in the infected wounds and accelerate their closure in a murine model, with negligible side effects on the normal tissues. Therefore, our G-Cu complexes may provide an efficient nonantibiotic alternative to the current treatments for bacterial infections.

Green Synthesis and Characterization of Silver Nanoparticles Using Flaxseed Extract and Evaluation of Their Antibacterial and Antioxidant Activities

Abstract: Bioactive plant chemicals are considered to be rich and useful for creating nanomaterials. The current work investigated the biosynthesis of silver nanoparticles (AgNPs) using ethanolic flaxseed extract as an efficient reducing factor. The production of AgNPs was verified by color-shifting observation of the mixture of silver nitrate (AgNO3) from yellow to a reddish suspension after the addition of the extract and by evaluating it by UV–visible inspection. Additionally, FTIR spectrum was used to support the identification of functional groups. The morphology and structure of AgNPs were assessed using scanning electron microscopy (SEM), and X-ray diffraction (XRD) examinations, which revealed spherical AgNPs with a diameter of 46.98 ± 12.45 nm and a crystalline structure. The zeta potential (ZP) and dynamic light scattering (DLS) measurements of AgNPs revealed values of −44.5 mV and 231.8 nm, respectively, suggesting appropriate physical stability. The antibacterial activity of AgNPs was investigated against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes, while the antioxidant effect was investigated using the DPPH technique. These obtained AgNPs could potentially be used as efficient antibacterial and antioxidant nanomaterials.