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Antimicrobial resistance--pharmacological solutions.

The interaction between microbial resistance and antibacterial agents occurs in a direct and an indirect fashion. Directly--through the development of resistance to the agent used, or to agents of the same class--as exemplified by the induction of beta-lactamase by both gram-positive and gram-negative bacteria. It also takes place through the development of resistance to compounds of different classes to the compound used, as exemplified by the loss of Streptococcus pneumoniae susceptibility to penicillin that is accompanied by a parallel loss of sensitivity to erythromycin and to tetracycline. As for the indirect way--microbial resistance may develop through selection of resistant organisms when the patient is treated with antibiotics, when the environment is contaminated with antibiotics (hospital) or when antibacterial agents are used in agriculture and animal husbandry.

Anti-Bacterial Agents↗

Some properties of Plesiomonas shigelloides treated with aminoglycosides.

The effect of aminoglycoside antibiotics (amikacin, gentamicin, netilmicin and tobramycin) at sublethal concentrations (sub-MICs) on some properties of Plesiomonas shigelloides strains was evaluated. All agents decreased the bacterial surface hydrophobicity. Amikacin (1/4 of the MIC) and netilmicin (1/4 and 1/8 of the MIC) changed the hydrophobic character of P. shigelloides surface to a hydrophilic one. Treatment of the strains with aminoglycosides decreased also motility, netilmicin being the most effective. No significant changes were found in lipolytic activity of antibiotic-treated strains. In the majority of cases aminoglycosides increased sensitivity of bacteria to hydrogen peroxide. The tested antibiotics did not induce production of short-chained N-acylhomoserine lactones signal molecules. Aminoglycosides at sub-MICs affected important activities of P. shigelloides potentially associated with their virulence in dependence on strain, antibiotic and concentration.

Amikacin↗

Effects of temperature and turbulence on the predator-prey interactions between a heterotrophic flagellate and a marine bacterium.

Biotic and abiotic factors can influence interactions between microbial grazers and their prey, thus impacting both the cycling of biogenic carbon within the surface layer of the ocean and the export of carbon to the deep ocean and higher trophic levels. In this study, microcosm experiments were used to evaluate the combined effect of temperature and turbulence on the growth rate of a marine bacterium (Vibrio splendidus), a protistan predator (Paraphysomonas sp.), and the community grazing impact of Paraphysomonas sp. on V. splendidus. It was found that the artificial turbulence generated (1.35 x 10-1 cm2 s-3) significantly increased the rates of growth of Paraphysomonas sp. at high (>10 degrees C), but not low (<5 degrees C) temperatures, and that turbulence had no effect on the growth of V. splendidus. Both flagellate and bacterial growth were temperature dependent and decreased 4- to 6-fold as temperatures decreased from 15 to 0 degrees C. Bacterial grazing mortality by Paraphysomonas sp. was 1.3- to 2.5-fold greater in the turbulent than static treatments among all four temperatures, and the rates of cell-specific ingestion of bacteria by Paraphysomonas sp. was 2-fold greater at 15 and 10 degrees C in the turbulent than in the static treatment. Hence, this study shows that turbulence can influence nanoflagellate grazing at temperatures >5 degrees C and suggests that at low temperatures, increased viscosity may limit the size of organisms that can be affected by small-scale turbulence.

Animals↗

Advancing the Deciphering of Host-Microbe Crosstalk with Spatial Omics: A Mini-Review.

Host-microbe crosstalk refers to the reciprocal influences between a host and its resident or invading microorganisms. This crosstalk plays important roles in maintaining host health, regulating physiological functions, and coordinating responses to infection. The rapid rise of spatial omics is transforming how this crosstalk is studied in both animals and plants. Unlike traditional bulk omics, which homogenize tissues and erase spatial context, spatial methods preserve in situ organization and can simultaneously capture molecular information from hosts and microbes. As a result, researchers can characterize the spatial organization of colonization and infection, identify spatial associations between microbial niches and host cell states, and visualize local host response gradients across intact tissues. Current spatial omics technologies encompass sequencing-based, imaging-based, and hybrid platforms. Spatial multi-omics approaches enable the joint measurement or integration of gene expression, protein abundance, and metabolite distributions. Although spatial association alone does not establish causality, spatial omics provides a high-resolution framework for characterizing host-microbe relationships within intact tissues and generating spatially constrained, testable hypotheses. When combined with perturbation experiments and complementary experimental evidence, these hypotheses can contribute to mechanistic interpretation of host-microbe crosstalk. Here, we review spatial omics technologies, compare their suitability and major trade-offs for host-microbe studies, and discuss computational strategies, analytical challenges, and future prospects.

Multiomics↗

Indigenous microbes and their soluble factors differentially modulate intestinal glycosylation steps in vivo. Use of a "lectin assay" to survey in vivo glycosylation changes.

It has been shown that Bacteroides thetaiotaomicron, a representative member of the gut microflora, signals intestinal epithelial cells both in vivo and in vitro and modulate specific glycosylation processes that may mediate intestinal functions. However it is not known whether these modulations depend on the presence of live bacteria or may be elicited by soluble factors produced in vitro by this bacterium. We used lectins and an histochemical approach to survey tissue sections prepared from various cellular compartments of the small and large intestine of NRMI/KI mice grown under gnotobiotic conditions. We compared the results obtained with bacterial culture supernatant and live B. thetaiotaomicron to those obtained from germ-free mice or mice having a conventional microflora. This approach allowed us to conclude that (1) a small but specific number of glycan patterns were restored after treatment with bacterial culture supernatant and (2) the B. thetaiotaomicron associated mice restored a larger number of patterns, however, the complete conventional mice pattern must be a function of the whole microflora in the gut. The possibility to modulate this complex glycosylation pattern by introducing exogenous bacteria and bacterial products should be considered as a promising approach towards understanding the molecular basis of microbial-host interactions.

Animals↗

Bacterial growth and substrate degradation by BTX-oxidizing culture in response to salt stress.

Interactions between microbial growth and substrate degradation are important in determining the performance of trickle-bed bioreactors (TBB), especially when salt is added to reduce biomass formation in order to alleviate media clogging. This study was aimed at quantifying salinity effects on bacterial growth and substrate degradation, and at acquiring kinetic information in order to improve the design and operation of TBB. Experiment works began by cultivating a mixed culture in a chemostat reactor receiving artificial influent containing a mixture of benzene, toluene, and xylene (BTX), followed by using the enrichment culture to degrade the individual BTX substrates under a particular salinity, which ranged 0-50 g l(-1) in batch mode. Then, the measured concentrations of biomass and residual substrate versus time were analyzed with the microbial kinetics; moreover, the obtained microbial kinetic constants under various salinities were modeled using noncompetitive inhibition kinetics. For the three substrates the observed bacterial yields appeared to be decreased from 0.51-0.74 to 0.20-0.22 mg mg(-1) and the maximum specific rate of substrate utilization, q, declined from 0.25-0.42 to 0.07-0.11 h(-1), as the salinity increased from 0 to 50 NaCl g l(-1). The NaCl acted as noncompetitive inhibitor, where the modeling inhibitions of the coefficients, K ( T(S)), were 22.7-29.7 g l(-1) for substrate degradation and K ( T(mu)), 13.0-19.0 g l(-1), for biomass formation. The calculated ratios for the bacterial maintenance rate, m (S), to q, further indicated that the percentage energy spent on maintenance increased from 19-24 to 86-91% as salinity level increased from 0 to 50 g l(-1). These results revealed that the bacterial growth was more inhibited than substrate degradation by the BTX oxidizers under the tested salinity levels. The findings from this study demonstrate the potential of applying NaCl salt to control excessive biomass formation in biotrickling filters.

Bacteria↗

Biological control of the size and reactivity of catalytic Pd(0) produced by Shewanella oneidensis.

The interaction between Shewanella oneidensis MR-1 and the soluble metal Pd(II) during the reductive precipitation of Pd(0) determined the size and properties of the precipitated Pd(0) nanoparticles. Assessment of cell viability indicated that the bioreduction of Pd(II) was a detoxification mechanism depending on the Pd(II) concentration and on the presence and properties of the electron donor. The addition of H(2) in the headspace allowed S. oneidensis to resist the toxic effects of Pd(II). Interestingly, 25 mM formate was a less effective electron donor for bioreductive detoxification of Pd(II), since there was a 2 log reduction of culturable cells and a 20% decrease of viable cells within 60 min, followed by a slow recovery. When the ratio of Pd:cell dry weight (CDW) was below 5:2 at a concentration of 50 mg l(-1) Pd(II), most of the cells remained viable. These viable cells precipitated Pd(0) crystals over a relatively larger bacterial surface area and had a particle area that was up to 100 times smaller when compared to Pd(0) crystals formed on non-viable biomass (Pd:CDW ratio of 5:2). The relatively large and densely covering Pd(0) crystals on non-viable biomass exhibited high catalytic reactivity towards hydrophobic molecules such as polychlorinated biphenyls, while the smaller and more dispersed nanocrystals on a viable bacterial carrier exhibited high catalytic reactivity towards the reductive degradation of the anionic pollutant perchlorate.

Biodegradation, Environmental↗

Effect of beta-lactamase inhibitors on the antimicrobial activity of cefoperazone, cefotaxime, and ceftizoxime against aerobic and anaerobic beta-lactamase producing bacteria.

Clavulanic acid (2.0 micrograms/ml) lowered the minimal inhibitory concentrations (MICs) of ceftizoxime and cefotaxime against 49 strains of the Bacteroides fragilis group by a mean of 4.0 and 3.4 log2 concentrations, respectively. Sulbactam plus ceftizoxime gave almost identical results. Sulbactam lowered cefoperazone MICs by a mean of 2 log2 concentrations. Against 52 aerobic and facultative isolates producing a variety of beta-lactamase types, the use of beta-lactamase inhibitors (sulbactam) was most effective in reducing the MICs of cefoperazone.

Bacteria, Aerobic↗

Entry of microbes into the host: using M cells to break the mucosal barrier.

Enteric microbial pathogens interact with the gut epithelium to establish infection. Recently, it has become clear that many microorganisms that colonize or traverse the intestinal mucosa do so via the specialized M cells. Recent work has shown that Shigella flexneri and Salmonella typhimurium specifically target M cells to initiate infection of the host.

Animals↗

Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery.

This article addresses the question of whether the uterine cavity is normally sterile and reviews the difficulties in conducting microbiologic studies of the endometrium, the limitations of conventional microbiologic techniques (cultivation-dependent), and the potential contribution of molecular microbiology to examine microbial diversity and burden of the endometrium. Issues pertaining to the diagnosis of chronic endometritis and the need for information about the prognostic value of this finding in subsequent pregnancies are discussed. The results of a randomized clinical trial of antibiotic administration versus placebo in women with a previous preterm birth are reviewed and commentary is provided. The emerging picture is that microbial-host interactions in the endometrial cavity are important for reproductive success. This is a US government work. There are no restrictions on its use.

Anti-Bacterial Agents↗

Effect of aqueous extract from Neem (Azadirachta indica A. Juss) on hydrophobicity, biofilm formation and adhesion in composite resin by Candida albicans.

OBJECTIVE: Azadirachta indica, a Meliaceae family tree, has been used in India for many years in the treatment of several diseases in medicine and dentistry. Current research analyses the effects of the leaf aqueous extract from Azadirachta indica (Neem) on the adhesion, cell surface hydrophobicity and biofilm formation, which may affect the colonisation by Candida albicans. METHODS: Azadirachta indica extract was tested in vitro on strains of Candida albicans 12A and 156B. Changes in hydrophobicity were reported in assays of yeast adhesion to hydrocarbons, in biofilm formation with glucose and in the adhesion of the microorganisms on light cured composite resin. Assays involved enumeration of candidal colony-forming units together with scintillation counting of radiolabelled Candida and compared to a solution of chlorhexidine digluconate 0.125% widely used in dentistry. RESULTS: Yeast growth in Neem extract was not inhibited in concentrations ranging from 0.1mg/ml. A statistically significant increase (p<0.05) in cell surface hydrophobicity was evident for the two strain tested and there was also an associated increase in biofilm formation after contact with Neem extract in concentration 0.01 g/ml. Decrease in adhesion capacity of cells to composite resin was also recorded. CONCLUSION: An anti-adhesive mechanism of action by Azadirachta indica is proposed based on the results observed.

Antifungal Agents↗

Antifungal properties of new series of quinoline derivatives.

The series of quinoline derivatives were prepared. The synthetic approach, analytical, and spectroscopic data of all synthesized compounds are presented. All the prepared derivatives were analyzed using the reversed-phase high performance liquid chromatography (RP-HPLC) method for the lipophilicity measurement. In the present study, the correlation between RP-HPLC retention parameter log K (the logarithm of capacity factor K) and various calculated log P data is shown. The relationships between the lipophilicity and the chemical structure of the studied compounds are discussed as well. The prepared compounds were tested for their in vitro antifungal activity. 2-[(3-Hydroxyphenylimino)methyl]quinolin-8-ol (8), 2-[(4-hydroxyphenylimino)methyl]quinolin-8-ol (9) and 2-[(2,5-dichloro-4-nitrophenylamino)methoxymethyl]quinolin-8-ol (10) showed in vitro antifungal activity comparable to or higher than that of the standard fluconazole. Structure-activity relationships among the chemical structure, the physical properties, and the biological activities of the evaluated compounds are discussed in the article.

Antifungal Agents↗

The introduction of fluorine atoms or trifluoromethyl groups in short cationic peptides enhances their antimicrobial activity.

The effect of introducing fluorine atoms or trifluoromethyl groups in either the peptidic chain or the C-terminal end of cationic pentapeptides is reported. Three series of amide and ester peptides were synthesised and their antimicrobial properties evaluated. An enhanced activity was found in those derivatives whose structure contained fluorine, suggesting an increase in their hydrophobicity.

Anti-Bacterial Agents↗

Sequence requirements and an optimization strategy for short antimicrobial peptides.

Short antimicrobial host-defense peptides represent a possible alternative as lead structures to fight antibiotic resistant bacterial infections. Bac2A is a 12-mer linear variant of the naturally occurring bovine host defense peptide, bactenecin, and demonstrates moderate, broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria as well as against the yeast Candida albicans. With the assistance of a method involving peptide synthesis on a cellulose support, the primary sequence requirements for antimicrobial activity against the human pathogen Pseudomonas aeruginosa of 277 Bac2A variants were investigated by using a luciferase-based assay. Sequence scrambling of Bac2A led to activities ranging from superior or equivalent to Bac2A to inactive, indicating that good activity was not solely dependent on the composition of amino acids or the overall charge or hydrophobicity, but rather required particular linear sequence patterns. A QSAR computational analysis was applied to analyze the data resulting in a model that supported this sequence pattern hypothesis. The activity of selected peptides was confirmed by conventional minimal inhibitory concentration (MIC) analyses with a panel of human pathogen bacteria and fungi. Circular-dichroism (CD) spectroscopy with selected peptides in liposomes and membrane depolarization assays were consistent with a relationship between structure and activity. An additional optimization process was performed involving systematic amino acid substitutions of one of the optimal scrambled peptide variants, resulting in superior active peptide variants. This process provides a cost and time effective enrichment of new candidates for drug development, increasing the chances of finding pharmacologically relevant peptides.

Amino Acid Sequence↗

A global survey of taxa-metabolic associations across mouse microbiome communities.

Host-microbiota mutualism is rooted in the exchange of dietary and metabolic molecules. Microbial diversity broadens the metabolite pool, with each taxon contributing distinct compounds in varying proportions. In the human microbiome, high variability in consortial composition is largely compensated by similar metabolic functions across different taxa. However, the extent of compensation in lower diversity mouse models, and whether vivaria are metabolically equivalent, is unknown. We provide a searchable resource of microbiome composition variability across 51 murine vivaria and 12 wild mouse colonies worldwide, with vivarium-specific variants mapped according to predicted 3D structures for each microbial species. Our matched metabolomics data show that realized metabolic potential has relatively low variability, providing functional evidence for metabolic compensation. Additionally, variability is related to taxonomic composition rather than vivarium, revealing taxa-metabolite associations that are potentially relevant to phenotypic differences between vivaria. Collectively, this resource offers tools to strengthen microbiome studies and collaborative science.

Animals↗

Contributions of the lipopolysaccharide outer core oligosaccharide region on the cell surface properties of Pseudomonas aeruginosa.

We have characterized the cell surface properties of three mutant series of Pseudomonas aeruginosa that show various defects in their lipopolysaccharide (LPS) core region. The deepest rough mutants of each series used in this study lacked completely rhamnose and glucose, and contained only galactosamine and alanine as LPS outer core constituents. However, rough mutants other than the deepest rough mutants showed high cell surface hydrophobicity compared to the corresponding parental strains, the deepest rough mutants showed less hydrophobicity than other rough mutants. The reactivity of an anti-lipid A monoclonal antibody with the deepest rough mutants was markedly higher than that with other counterparts. The deepest rough mutants tended to be more susceptible to antibiotics, such as gentamicin and polymyxin B, than the corresponding parental strains and other rough mutants. The above evidence indicates that neutral sugar, namely rhamnose and glucose, residues of the LPS outer core region play a critical role in the cell surface properties of P. aeruginosa.

Anti-Bacterial Agents↗

Biological and physicochemical properties of gemini quaternary ammonium compounds in which the positions of a cross-linking sulfur in the spacer differ.

We synthesized two novel gemini quaternary ammonium compounds (gemini QACs), 4,4'-[1,6-(2,5-dithiahexane)]bis(1-alkylpyridinium bromide) and 4,4'-[1,6-(3,4-dithiahexane)]bis(1-alkylpyridinium bromide), which are essentially two dimerized pyridinium salts. Three gemini QACs in which the positions of a cross-linking sulfur in the spacer differ, in addition to the previously described 4,4'-[1,6-(1,6-dithiahexane)]bis(1-alkylpyridinium bromide) to both gemini compounds, were determined for their antimicrobial, hemolytic and surface activities and molecular hydrophobicity. Comparative biological and physicochemical studies concluded that the position of sulfur in the spacer chain for three gemini QAC series influences the surface activity, the hydrophobicity and the electron density of the ammonium nitrogen, and that their biological properties are ascribable to the variation of these parameters caused by the position of the sulfur.

Anti-Bacterial Agents↗

Benzenesulfonamide analogs of fluoroquinolones. Antibacterial activity and QSAR studies.

The structure-activity relationships (SAR) of new antibacterial benzenesulfonamidefluoroquinolones (BSFQs), coming from derivatization of N4-piperazinyl of ciprofloxacin (CIP) were studied. The behavior of the new BSFQ series was similar to the previously norfloxacin (NOR) analogs reported, making possible a quantitative structure-activity relationships (QSAR) analysis of the complete set of BSFQs. The presence of the benzenesulfonylamido (BS) groups shifted the activity of classic antimicrobial fluoroquinolones from being more active against Gram-negative to Gram-positive strains. QSAR studies through Hansch analysis showed a linear correlation of the activity with electronic and steric parameters. Small electron-donor groups would increase the in vitro activity against Gram-positive bacteria. Hydrophobic properties played a minor role when activity is measured as minimum inhibitory concentration (MIC). QSAR analysis also reinforces previous biological findings about the presence of new interactions with target topoisomerases.

Anti-Bacterial Agents↗