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Isolation of a new antibiotic 333-25, related to antibiotic EM 49. (Studies on antibiotics from the genus Bacillus. XI).

A new antibiotic, 333-25, active against Gram-positive and Gram-negative bacteria, was isolated from the culture broth of Bacillus circulans 333-25. The antibiotic is a basic acylpeptide containing 2,4-diaminobutyric acid (5), leucine (2), phenylalanine (1) and a fatty acid. It is closely related to antibiotic EM 49, but can be differentiated by chromatographic behaviour.

Animals

Neo-enactin, a new antifungal antibiotic potentiating polyene antifungal antibiotics. II. Taxonomic studies of the producing microorganism and simultaneous production of bleomycin group and streptothricin-like antibiotics.

A new antifungal antibiotic, named neo-enactin, was produced mainly in the mycelia of strain H 829-MY 10. Strain H 829-MY 10 was identified as a Streptoverticillium, determined to be nonchromogenic, and fits in the white color-series. Although Streptoverticillium olivoreticuli is known to be chromogenic, strain H 829-MY 10 is most related to that species. Thus, strain H 829-MY 10 is named as Streptoverticillium olivoreticuli subsp. neoenacticus. Besides neo-enactin, two bleomycin-group antibiotics and two streptothricin-like antibiotics were simultaneously produced by strain H 829-MY 10.

Anti-Bacterial Agents

Occurrence of antibiotic-resistant E. coli and antibiotic resistance genes from culturable bacteria in drinking water sources along the Upper Mahaweli River, Sri Lanka.

Antibiotic-resistant Escherichia coli (AR-E. coli) and antibiotic resistance genes (ARGs) in aquatic environments pose a serious threat to public health. However, their presence in river water in South Asian countries is not well established. The present study investigated AR-E. coli and ARGs from culturable bacteria in drinking water sources from 14 drinking water treatment plants situated along the Upper Mahaweli River, a tropical central hill-country river system in Sri Lanka. A total of 167 E. coli isolates were tested against ten antibiotics using the Kirby-Bauer method, and genomic DNA from culturable bacteria in 45 water samples were screened for 11 ARGs using PCR. Overall, 60.48% E. coli isolates exhibited resistance to at least one antibiotic and multidrug resistance was detected in 27.54%. Highest resistance was for amoxicillin (47.31%), tetracycline (26.95%), and co-trimoxazole (24.55%) and four antibiotics showed seasonal variation. ARGs, dominated by blaTEM (80.0%), tetA (66.67%), and tetM and qnrS (62.22%) were detected in 42.42% PCR assays (n = 210). Multiple antibiotic resistance index varied from 0.00 to 0.80, with 44.91% exceeding the 0.2 threshold value, and the antibiotic resistance index varied from 0.00 to 0.32, with eight above the threshold (≥ 0.2). Hierarchical cluster analysis grouped majority of drinking water sources into the intermediate category while few were categorized under low (Kotagala and Thalawakelle-Galkanda) and high (Haragama, Paradeka, and Nawalapitiya), reflecting the variability of anthropogenic interference. Results highlight the risk associated with AR-E. coli and ARGs from culturable bacteria in one of Sri Lanka's key drinking water sources. Proactive interventions ensuring long-term safety of drinking water sources are urgently needed to safeguard public health.

Sri Lanka

The fate of antibiotics and antibiotic resistance genes in Large-Scale chicken farm Environments: Preliminary view of the performance of National veterinary Antimicrobial use reduction Action in Guangdong, China.

In 2018, China implemented the Veterinary Antimicrobial Use Reduction Action to curb the rapid development of antibiotic resistance (AR). However, the AR-related pollutions in animal farms after the reduction policy has been poorly investigated. Here, we performed a comprehensive investigation combining UPLC-MS/MS, metagenomic, and bacterial genomic analyses in eight representative large-scale chicken farms in Guangdong, China. Our results showed that antibiotics and ARGs contaminations were more severe in broiler farms than in layer farms. Notably, diverse tet(X) variants were prevalent in the chicken farms. These tet(X)s was carried by diverse E. coli lineages and obviously correlated with ISCR2 and IS1B transposases. The resistomes in chicken farms was significantly correlated with microbial community, and multiple factor analyses indicated that the joint effect of antibiotics-microbial community-MGEs was the most dominant driver of ARGs. Host tracking identified a variety of ARG bacterial hosts and the co-occurrence of ARGs-MRGs-MGEs. Source tracking indicated that the inherent component represented the main feature of resistomes in different hosts, while ARG transfer between the chicken gut and farm environments were frequent. A multiperspective evaluation of AR risk revealed that the early effect of antibiotic reduction was exhibited by the mitigation of maximum level of risky ARGs, prevalence of environmental AR pathogens, and HGT potential of ARGs mediated by phage structures. Overall, our findings provide insights into the antibiotic and ARG profiles in large-scale chicken farms with different rearing strategies and demonstrate a preliminary view of the performance of antibiotic reduction actions in China.

Chickens

Sequential antibiotic exposure restores antibiotic susceptibility.

BACKGROUND: The prevalence of antibiotic resistance continues to rise, rendering many valuable antimicrobial drugs ineffective. Pairwise cyclic antibiotic therapy, where treatment is rapidly switched between two antibiotics, has been demonstrated in vitro to limit the evolution of antibiotic resistance. However, what happens when resistance inevitably evolves to one of the drugs? METHODS: In this study, we perform over 450 evolution experiments to test the resilience of four proposed cyclic therapies. We use soft agar gradient evolution and 'flat plates' to identify resistance trade-offs that are resilient to compensatory mitigation. Resensitizations were detected by antimicrobial susceptibility assays, and their mechanistic underpinnings were elucidated via genomic and phenotypic analyses. RESULTS: Resistance evolves readily and collateral sensitivity (CS) (where resistance to drug A leads to hypersensitivity to drug B) does not hinder the evolution of multidrug resistance and does not predict or promote resensitization. However, if resistance to drug B increases susceptibility to A, a phenomenon we term backward CS, resistance to A can be reduced or even reversed. For example, we show that Escherichia coli cells frequently become hypersensitive to β-lactams upon aminoglycoside resistance acquisition, due to conflicting modifications to the proton motive force and efflux pumps. We also find for the first time that polymyxin B resistance can be entirely reversed by exposure to tigecycline, through the acquisition of compensatory mutations that reduce the fitness penalty of tigecycline resistance. CONCLUSIONS: The longevity of drug cycling protocols can be significantly improved by leveraging backwards CS to resensitize cells as antibiotic resistance evolves.

Anti-Bacterial Agents

Morphology of experimental antibiotic-associated enterocolitis in the hamster: a model for human pseudomembranous colitis and antibiotic-associated diarrhoea.

The morphology of antibiotic-associated enterocolitis in the hamster is described and compared with human antibiotic-associated pseudomembranous colitis. It is shown to be a caecal disease with proliferative mucosal changes and in this respect unlike the human counterpart. The bacteriology and toxicology, however, are identical. In addition, mucosal changes are described in animals on antibiotics but without established enterocolitis. As a result we suggest that there may be a spectrum of human disease ranging from mild antibiotic-associated diarrhoea to established pseudomembranous colitis. Therefore, despite the morphological variation, the hamster remains a good model for investigating the pathogenesis of pseudomembranous colitis and antibiotic-associated enteropathy in general.

Animals

Antiviral antibiotic S15-1. Taxonomy of the producing strain and study of conditions for production of the antibiotic.

Strain S15-1 which produces antiviral antibiotic S15-1 belonging to the streptothricin group of antibiotics was isolated from a soil sample. Cell analysis, colony morphology, the absence of sporangia-like vesicles, the formation of spores in chains of the Rectus Flexibilis type, and the ability to produce melanoid pigment, indicate that this strain belongs to the genus Streptomyces Waksman and Henrici. A comparison of the characteristics of strain S15-1 with related Streptomyces show that it should be identified as Streptomyces purpeofuscus Yamaguchi and Saburi. The investigation of cultural conditions show that soluble starch and meat extract are the most suitable carbon and organic nitrogen sources for the production of antibiotic S15-1. Strain S15-1 grew poorly on media with no organic nitrogen sources, and did not produce the antibiotic. Antiviral antibiotic S15-1 is accumulated at the highest level after 3 or 4 days growth of the producing organism.

Anti-Bacterial Agents

Neo-enactin, a new antifungal antibiotic potentiating polyene antifungal antibiotics. I. Fermentation, extraction, purification and physico-chemical and biological properties.

A new antifungal antibiotic, named neo-enactin, was isolated from the cultured mycelia of Strain H 829-MY 10, identified as a new subspecies of Streptoverticillium and named Streptoverticillium olivoreticuli subsp. neoenacticus. The antibiotic was produced with a tetraene antifungal antibiotic, found mainly in the cultured mycelia of Strain H 829-MY 10 and it was extracted with methanol. The antibiotic is of a basic nature and it can be extracted with ethyl acetate at alkaline pH. Purification of neo-enactin was carried out by partition chromatography on cellulose and elution with ethyl acetate bufferized with phosphate buffer (pH 8.0). Neo-enactin shows strong antifungal activity and potentiates the antifungal activity of polyene antifungal antibiotics.

Antifungal Agents

Nationwide survey of antibiotic resistance by means of a computer. An introduction into the analysis of multiple antibiotic resistance.

One-year surveillance of single and multiple antibiotic resistance of 8 species of so-called "Problem Bacteria" by computer analysis of data obtained from 18 Public Health Laboratories in Slovakia in 1973 enables to establish the most frequently occuring spectra of multiple drug resistance which would point to the spread of typical R plasmids among the Problem bacteria investigated. As an introduction, we surveyed the mode of testing of Problem bacteria in individual PHLs against antibiotics - drugs of choice. Iw was important to find out whether strains belonging to Problem bacteria investigated are tested against sufficient number of antibacterial drugs. Our study shows that the percentage of bi- and multiple drug resistance in almost all bacterial species investigated depend on the number of antibiotics used in tests in vitro as single discs. The more antibiotic discs are used to test the strains, the more chance the laboratory has to register the true picture of multiresistance to antibiotics. Our study also shows that the testing in the PHLs associated to the computer study in this respect is inadequate. Moreover, the increasing complexity and proportion of multiple drug resistance in Problem Bacteria - with a notable exception of Salmonellae - forces the PHLs to use more and more discs so that using two Petri dishes full of discs - 12 to 15 discs - begins to be necessary in testing of most of the Problem bacteria under investigation.

Anti-Bacterial Agents

Oral antibiotic therapy for skeletal infections of children. I. Antibiotic concentrations in suppurative synovial fluid.

To evaluate the feasibility of oral antibiotic treatment for pyogenic arthritis, one or more oral doses of antibiotics were substituted for the drugs being used for parenteral therapy. Synovial fluid and serum specimens obtained at randomized times after an oral dose of ampicillin, cephalexin, cloxacillin, dicloxacillin, or penicillin G were assayed for antibiotic content and antibacterial activity. Seventy specimens from 21 infants and children were studied. Peak synovial fluid concentrations were greater than 60% of peak serum concentrations with all drugs tested and there was adequate inhibitory activity against bacteria commonly causing arthritis. The degree of antibiotic binding to serum protein had no apparent effect on the degree of penetration into pyogenic synovial fluid.

Administration, Oral

Aminoglycoside-modifying enzyme of an antibiotic-producing bacterium acts as a determinant of antibiotic resistance in Escherichia coli.

Bacillus circulans NRRL B-3312, a nonpathogenic bacterium that produces the aminoglycoside antibiotic butirosin, is known to contain an aminoglycoside phosphotransferase that is similar to the neomycin phosphotransferases of clinically isolated antibiotic-resistant bacteria. Purified DNAs from B. circulans and the plasmid ColE1-ApR were digested with EcoRI endonuclease and the resulting fragments covalently joined with polynucleotide ligase. The recombined DNA was used to transform E. coli and ampicillin-neomycin resistant colonies were selected. Analysis of several clones indicated that neomycin resistance in the E. coli transformants was due to the presence of the B. circulans phosphotransferase gene. This observation is consistent with the notion that anitbiotic-modifying enzymes from antibiotic-producing organisms may be the sources of antibiotic resistance in plasmid-containing bacteria.

Bacillus

Use of sodium polyanethol sulfonate to selectively inhibit aminoglycoside and polymyxin antibiotics in a rapid blood level antibiotic assay.

Sodium polyanethol sulfonate inhibits aminoglycoside and polymyxin classes of antibiotics in direct proportion to its concentration. Aminoglycoside and polymyxin class antibiotics are selectively inactivated; penicillin, including the semisynthetic penicillins, cephalothin, chloramphenicol, clindamycin, tetracycline, erythromycin, and vancomycin are not inhibited. By incorporating sodium polyanethol sulfonate directly into the test medium it is possible, in a 4-h antibiotic blood level assay, to selectively obviate the activity of the aminoglycosides and polymyxins to determine the concentration of other antibiotics present in the same serum sample.

Aminoglycosides

Antibiotic DE-3936, a polyether antibiotic identical with lonomycin. Taxonomy, fermentation, isolation and characterization.

Antibiotic DE-3936 was isolated from the fermentation broth of a streptomycete No. 9735-1, which is identified as a strain of Streptomyces hygroscopicus. The antibiotic is a hydrophobic compound having the molecular formula of of C44H75O14Na and is active against Gram-positive bacteria, mycobacteria, mycoplasma and protozoa, especially coccidia. Its chemical and biological properties indicate that antibiotic DE-3936 belongs to the group of polyether antibiotics and is identical with lonomycin.

Animals

Comparative randomized study of protected environment plus oral antibiotics versus oral antibiotics alone in neutropenic patients.

A series of 24 patients with severe neutropenia, most of whom had acute myeloblastic leukemia, were treated in an isolation unit with oral nonabsorbable antibiotics and were compared to 21 similar patients receiving oral antibiotics alone. The frequency of bacterial infections was lower in the patients receiving both isolation and oral antibiotics compared to the patients who received only oral antibiotics. The responses to chemotherapy in terms of remission rates were identical for the two groups.

Adolescent

Micro-interfacial behavior of antibiotic-resistant bacteria and antibiotic resistance genes in the soil environment: A review.

Overutilization and misuse of antibiotics in recent decades markedly intensified the rapid proliferation and diffusion of antibiotic resistance genes (ARGs) within the environment, thereby elevating ARGs to the status of a global public health crisis. Recognizing that soil acts as a critical reservoir for ARGs, environmental researchers have made great progress in exploring the sources, distribution, and spread of ARGs in soil. However, the microscopic state and micro-interfacial behavior of ARGs in soil remains inadequately understood. In this study, we reviewed the micro-interfacial behaviors of antibiotic-resistant bacteria (ARB) in soil and porous media, predominantly including migration-deposition, adsorption, and biofilm formation. Meanwhile, adsorption, proliferation, and degradation were identified as the primary micro-interfacial behaviors of ARGs in the soil, with component of soil serving as significant determinant. Our work contributes to the further comprehension of the microstates and processes of ARB and ARGs in the soil environments and offers a theoretical foundation for managing and mitigating the risks associated with ARG contamination.

Soil Microbiology

Colorimetric determination of peptide antibiotics: in-process assay of cyclic octapeptidic antibiotics in fermentation broths.

A spectrophotometric method is presented for monitoring the biosynthesis of a new complex of cyclic octapeptidic antibiotics in fermentation broths. The method is based on the extraction of antibiotic from alkaline broth with butanol. An ion-pair, formed between the octapeptides and bromthymol blue, is extracted into chloroform from a solution buffered to pH 7.5. The absorbance of the colored solution is measured at 420 nm. Results are in good agreement with those obtained by microbiological assay. The method is also applicable to other peptidic antibiotics such as polymyxin B and gramicidin.

Anti-Bacterial Agents