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PubMed1978

Erythromycin resistance and the chloroplast ribosome in Chlamydomonas reinhardi.

Five classes of erythromycin-resistant mutants of Chlamydomonas reinhardi have been identified. Each class corresponds to a different genetic locus, three nuclear and two chloroplast. The three nuclear loci appear to be unlinked, while Conde et al. (1975) have shown that the two chloroplast loci are linked, but not allelic. Mutants in each class have a unique pattern of cross-resistance in vivo to other antibiotics (lincomycin, carbomycin, and cleocin) that affect chloroplast protein synthesis. The chloroplast ribosomes from each class have a distinctive erythromycin-binding reaction in vitro.--Haploid and diploid strains containing combinations of different genes affecting the chloroplast ribosome were constructed to probe ribosome structure. New phenotypes were obtained by such combinations, demonstrating interactions between the gene products of a number of loci specifying ribosome components.

Chlamydomonas↗
PubMed1976

Laboratory findings of tobramycin and their relation to clinical response.

The susceptibilities of various clinical isolates to tobramycin were studied, and the applicability of these data to clinical situations was evaluated. The bactericidal nature of tobramycin was confirmed by killing curves, and the minimal inhibitory concentrations for 500 common pathogens were used to define its spectrum. Isolates inhibited by less than or equal to 5 mug/ml were considered to be sensitive to tobramycin. The clinical response of some patients was examined in relation to the minimal inhibitory concentration for the infecting organism and the serum and urine levels of tobramycin. The activity of tobramycin was compared with that of gentamicin against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Tobramycin was at least twice as active as gentamicin against P. aeruginosa. The effectiveness of tobramycin against S. aureus and E. coli was compared with that of other commonly used antibiotics, and its clinical role as an alternative to gentamicin in the "best guess" treatment of septicemia was considered. Lincomycin is often added to counter the ineffectiveness of tobramycin against streptococci and anaerobes such as Bacteroides species, but this combination was antagonistic against E. coli when tested in vitro by the checkerboard technique and its graphical display, the isobologram. Tobramycin was essentially similar to gentamicin in laboratory characteristics and clinical application but was more active against P. aeruginosa in general and against gentamicin-resistant strains in particular.

Anti-Bacterial Agents↗
PubMed1983

Effects of subinhibitory antibiotics on bactericidal activity of chronic granulomatous disease granulocytes in vitro.

Experiments were performed on leukocytes from patients with chronic granulomatous disease (CGD), incubated with subinhibitory concentrations of antibiotics (clindamycin, methicillin and N-demethyl-lincomycin). Results indicate a minor enhancement of bactericidal activity. This improvement occurred in both CGD homozygotes and one heterozygote and may indicate a future role for the use of low dose antibiotics to augment immune defences such as granulocyte function.

Anti-Bacterial Agents↗
PubMed1985

Determination of the activity on Legionella of eight macrolides and related agents by comparative testing on three media.

It has proved difficult to develop a standard method for the determination of minimum inhibitory concentrations (MICs) of antibiotics against the Legionellaceae. A major obstacle has been the inactivation of certain antibiotics by components of Charcoal Yeast Extract agar, especially charcoal. To determine the MICs of eight macrolides and related agents (erythromycin, spiramycin, oleandomycin, josamycin, midecamycin, lincomycin, clindamycin and pristinamycin) for 36 strains of Legionella, we used two charcoal-free media: Buffered Yeast Extract agar and Buffered Antibiotic Medium no. 1 (BAM1), the latter having been developed in our own laboratory. The inhibitory effect of charcoal was most marked on josamycin and pristinamycin. This effect was absent on the charcoal-free media, which both, however, inhibited spiramycin. BAM1 agar seemed the better of the two charcoal-free media as it gave more consistent growth. The most active agents were josamycin (0.06-0.25 mg/l), pristinamycin (0.06-0.5 mg/l) and erythromycin (0.12-0.5 mg/l). Midecamycin (0.12-1 mg/l) and spiramycin (1-5 mg/l) also had useful activity.

Anti-Bacterial Agents↗
PubMed1985

Structure activity relationships in lincosamide and streptogramin antibiotics.

Lincomycin is a 6-amino, 6-deoxy-octopyraninose with strong antibiotic activity. To maintain or enhance this activity, one must have the configuration of the first five asymmetric carbons of the sugar residue with the thioglycolic moiety in the alpha-position. The nitrogen on carbon 6 with the R configuration is also a prerequisite for the activity. Substitutions at the level of C-7 as well as the pyrolidine moiety can dramatically enhance this activity. The streptogramin group is composed of a wide variety of structures which can be classified into two subgroups. Group A or M is composed of polyunsaturated cyclic peptolides, e.g. pristinamycin IIA; group B or S is composed of cyclic hexadepsipeptides. Separately, these molecules have a bacteriostatic activity on Gram-positive organisms, whereas in association they exhibit a strong and synergistic bactericidal effect. The 13-OH function of PIIA is essential for antibiotic activity to occur whereas the 15-carbonyl function can be reduced with the retention of the biological properties of the drug. The carbonyl function of PIA can be reduced and the pipecolic moiety can be replaced by other groups without a dramatic influence on the antibiotic activity. The macrocyclic lactone ring is necessary for antibiotic activity.

Acetylation↗
PubMed1986

The neutralization of antibiotic action by metallic cations and iron chelators.

The neutralization of the action of a variety of antibiotics on klebsiellae by moderate doses of di- and tri-valent metallic cations, was measured in vitro. Some beta-lactams tested were affected by Mg++ and by Cu++. Of six tetracyclines one was moderately neutralized by Ca++, two by Mg++, three by Cu++, and all, strongly, by Fe+++. Erythromycin was affected by Ca++, lincomycin by Ca++, Mg++ and Cu++. Aminoglycosides were affected by Ca++ and Mg++ and strongly by Fe+++. Five antibiotics (three beta-lactams and two macrolides) with high MICs for klebsiellae were tested against staphylococci: most of the reversing agents were ineffective. The microbial iron chelators, desferrioxamine and enterochelin were largely inactive, affecting only two aminoglycosides.

Anti-Bacterial Agents↗
PubMed1986

The quantification of the neutralization of the action of antibiotics by cationic iron.

This paper describes the reversal of antibiotic action by iron. Crude measurements of the molar ratio of iron to various antibiotics at reversal indicated that ampicillin, carbenicillin and lincomycin had low ratios of 0.2 to 2.4. With the remainder the ratios lay between 13 and 105; they averaged 46 for the tetracyclines, and 70 for the aminoglycosides. Precise measurement with Fe+++ and tetracycline revealed that the molar ratio for neutralization increased with increasing concentrations of tetracycline; from 1 to 625 mg/l the ratio increased over three-fold from 35 to 118. At the tetracycline concentration of 5 mg/l--usually achieved in plasma during effective therapy--the ratio is of the order of 45.

Aminoglycosides↗
PubMed1992

Antibiotic sensitivity of ribosomes from wild-type and clindamycin resistant Bacteroides vulgatus strains.

The sensitivity to different antibiotics of in-vitro polyuridylic acid-dependent polypeptide synthesizing system from Bacteroides vulgatus RYC18F6 and two clindamycin-resistant derivatives was studied. The ribosomes from the resistant strains were not affected by concentrations of up to 0.1 mM clindamycin and lincomycin. In contrast, streptogramin B was found to cause strong stimulation of the clindamycin-resistant polymerizing systems. The modified ribosomes from the resistant strains were more sensitive to other antibiotics like sparsomycin and chloramphenicol. The data indicate that resistance in these B. vulgatus mutant strains is due to alteration of the ribosome structure.

Bacteroides↗
PubMed1995

In-vivo transfer of resistance plasmids in rat, human or pig-derived intestinal flora using a rat model.

Germ-free rats associated with either rat- (RIF), human- (HIF) or pig-(PIF) derived Enterobacteriaceae-free intestinal flora were used for in vivo experiments to detect transfer of antibiotic resistance. Transfer of resistance was observed most frequently from the porcine donor strain to acceptor strain Escherichia coli K12, showing the highest number of transconjugants in the faeces of HIF-rats. The rats associated with the human donor strain and E. coli K12 as acceptor showed transconjugants less frequently. Only the HIF-rats yielded transconjugants on each sampling day and none at all could be isolated from the PIF-rats. Almost no transconjugants were found in the faeces of rats associated with the pig donor strain and a wild human E. coli strain as acceptor. Factors such as the nature of the donor and recipient strains as well as the origin of the intestinal flora seemed to have an influence on plasmid transfer. Transferability was highest in the HIF-rats and could be increased by administration of lincomycin. This study showed that in vivo transfer of resistance plasmids is possible in rats associated with intestinal floras of different origins. The human intestinal flora seemed to permit better transfer of resistance than that derived from the pig or the rat.

Animals↗
PubMed2004

A new phenotype of resistance to lincosamide and streptogramin A-type antibiotics in Streptococcus agalactiae in New Zealand.

OBJECTIVES: To characterize a new type of resistance to clindamycin in Streptococcus agalactiae. METHODS: Nineteen erythromycin-susceptible, clindamycin-resistant S. agalactiae isolates from New Zealand were studied. MICs of macrolide, lincosamide and streptogramin antibiotics were determined. Clindamycin and streptogramin resistance genes were searched for by PCR. Isolates were compared by serotyping and by DNA macrorestriction patterns determined by PFGE. Conjugative transfer of resistance traits to recipient strains of S. agalactiae and Enterococcus faecium was assayed. RESULTS: The 19 S. agalactiae isolates were intermediate or resistant to clindamycin (MIC range: 0.5-2 mg/L) and lincomycin (MIC range: 1-8 mg/L) and had high MICs of dalfopristin (4-32 mg/L), a streptogramin A-type antibiotic, compared with controls. By contrast, the strains were susceptible to macrolides and quinupristin, a streptogramin B-type antibiotic. This new phenotype was called LSA (lincosamide-streptogramin A). Clindamycin resistance could not be transferred to recipient strains. Thirteen isolates belonged to serotype III and to a single PFGE genotype A, and five isolates belonged to serotype I and to genotype B. One isolate was non-typeable and belonged to a distinct genotype C. CONCLUSIONS: We have characterized a new LSA phenotype in S. agalactiae. Analysis of restriction patterns of S. agalactiae chromosomal DNA showed that the resistance was spread in a minimum of three bacterial clones. The genetic and biochemical basis for the resistance remains unknown.

Adult↗
PubMed2003

Observations on the history of the development of antimicrobials and their use in poultry feeds.

Antimicrobials are powerful tools, but controversy and conflict often follow power. The development of antimicrobials was marked by personal attacks, political intrigue, internal conflicts, and lawsuits. Such controversy and conflict has continued. The early history of supplementing animal feeds with antimicrobials parallels the isolation and identification of vitamin B12. Vitamin B12 was isolated and characterized in 1948, but further research showed that several feed ingredients, including dried mycelia of certain fungi, were more potent as growth promoters in the diet of chicks than was vitamin B12 alone. The growth-promoting component in fungal mycelia was shown to have antimicrobial activity. A total of 32 antimicrobial compounds are approved for use in broiler feeds in the U.S. without a veterinary prescription. Fifteen compounds are listed for treatment of coccidiosis, 11 are listed as growth promotants, and six are listed for other purposes. Seven compounds are also used in human medicine. These compounds include bacitracin, chlotetracycline, erythromycin, lincomycin, novobiocin, oxytetracycline, and penicillin. No published estimates of antimicrobial use in animals exist at present, and estimates of that use differ markedly. The Union of Concerned Scientists (UCS) estimates usage at 30.6 million pounds, nearly 50% (49.85%) higher than the Animal Health Institute (AHI) estimate of 20.42 million pounds. AHI surveyed their members (the manufacturers of antimicrobials) to obtain their estimates, whereas USC calculated their estimates using published data and the following general formula: antimicrobial use = number of animals treated x average days treated x average dose.

Animal Feed↗
PubMed2005

Antimicrobial susceptibility of environmental Staphylococcus aureus strains isolated from a pigeon slaughterhouse in Italy.

No information is available concerning the antimicrobial susceptibility of Staphylococcus aureus isolated from pigeon slaughterhouses. In the present study, 59 staphylococcal strains isolated from a pigeon slaughterhouse in central Italy were compared according to their antibiotic resistance. On the basis of cultural and biochemical properties, all isolates could be identified as S. aureus. The strains were checked for the productions of enterotoxins A, B, C, D by reversed passive latex agglutination. Resistance to 26 antibiotics was also determined paying particular attention to resistance to those antimicrobial agents frequently used in human medicine and in poultry breeding. Only one strain was positive for the production of enterotoxins type C and D. It was isolated from the evisceration tube after slaughtering. Enterotoxin B was produced by 2 strains isolated from the eyebrows and conjunctivas of the worker operating the crop rinsing tube. As to the susceptibility to antibiotics, all strains were sensitive to amoxicillin/clavulanic acid, bacitracin, cephalothin, fusidic acid, gentamicin, kanamycin, linezolid, oxacillin, quinupristin/dalfopristin, rifampicin, tobramycin, trimethoprim-sulfamethoxazole, vancomycin. Some (15.2%) of the strains were resistant to ampicillin and to penicillin G; 6.8% were resistant to chloramphenicol, 20.3% to enrofloxacin, 16.9% to erythromycin and to ciprofloxacin, 8.5% to clindamycin, and 11.9% to lincomycin. The highest percentages of strains were resistant to tetracycline and oleandomicin (37.3 and 25.4% respectively). Methicillin-resistant staphylococci were also found (3.4%). Only one strain had a multiple antibiotic resistance index > 0.30. The results were statistically analyzed and clustered in 6 groups. This work provides the antibiotic resistance pattern of S. aureus strains isolated from a pigeon slaughtering plant and represents a study on a quite unknown field in meat production.

Abattoirs↗
PubMed1994

Decline of erythromycin resistance of group A streptococci in Japan.

Six hundred seventy isolates from children with Group A streptococcal infections from 1981 through 1990 were typed serologically and their antibiotic susceptibilities were determined. There were 479 isolates from patients with pharyngitis, 133 from those with scarlet fever, 35 from those with suppurative infection and 23 from those with nonsuppurative disease. The prevalent M serotypes were 12, 4, 1, 3 and 28. None of the 670 isolates were resistant to penicillin G and cephalexin. Resistance rates of isolates to erythromycin and lincomycin was 22.2% in 1981 and 1982, but a marked decrease was noted after 1983 and only one has been resistant since 1986. Nineteen of 21 erythromycin-resistant isolates were M type 12, and two others were M types 4 and 28. Chloramphenicol resistance was similar to that of erythromycin, and the tetracycline resistance rate decreased gradually from 60% to less than 20%.

Adolescent↗
PubMed1976

Eikenella corrodens osteomyelitis, arthritis, and cellulitis of the hand.

Eikenella corrodens was isolated from an orally contaminated hand wound which resulted in cellulitis, osteomyelitis, and arthritis. E corrodens is a gram-negative, microaerophilic bacillus which only lately has received attention as a possible pathogen. The organism grows characteristically as small, corroding, or pitting colonies on blood agar. It typically requires hemin or blood for reliable aerobic growth. Oral contamination of wounds predisposes to infection with E. corrodens. The management of these infections includes treatment with an effective antibiotic and surgical debridement. Because it is gram-negative, microaerophilic, and often difficult to isolate, infections caused by E corrodens may mimic those caused by gram-negative obligate anaerobes. However, E corrodens is resistant to clindamycin and lincomycin and sensitive to most other commonly used antimicrobial agents.

Adult↗
PubMed1977

Fatal colitis in a hemophilic patient with inhibitor.

A severe colitis developed in a hemophilic patient following an antibiotic regimen which included clindamycin. A surgical procedure, total hip replacement, had been complicated by the appearance of a powerful factor VIII inhibitor and a Bacteroides fragilis infection. The resulting bleeding diathesis was successfully managed with the use of an "activated prothrombin complex"; however, the occurrence of colitis following intravenous clindamycin therapy proved to be fatal. Clindamycin, like the related antibiotic lincomycin, appears to have significant intestinal toxicity and should be restricted to the treatment of life-threatening proven Bacteroides infections.

Adult↗
PubMed2003

Coordination of plastid and nuclear gene expression.

The coordinated expression of genes distributed between the nuclear and plastid genomes is essential for the assembly of functional chloroplasts. Although the nucleus has a pre-eminent role in controlling chloroplast biogenesis, there is considerable evidence that the expression of nuclear genes encoding photosynthesis-related proteins is regulated by signals from plastids. Perturbation of several plastid-located processes, by inhibitors or in mutants, leads to decreased transcription of a set of nuclear photosynthesis-related genes. Characterization of arabidopsis gun (genomes uncoupled) mutants, which express nuclear genes in the presence of norflurazon or lincomycin, has provided evidence for two separate signalling pathways, one involving tetrapyrrole biosynthesis intermediates and the other requiring plastid protein synthesis. In addition, perturbation of photosynthetic electron transfer produces at least two different redox signals, as part of the acclimation to altered light conditions. The recognition of multiple plastid signals requires a reconsideration of the mechanisms of regulation of transcription of nuclear genes encoding photosynthesis-related proteins.

Carotenoids↗
PubMed2001

Shewanella japonica sp. nov.

Two strains of agar-digesting bacteria, KMM 3299T and KMM 3300, respectively isolated from sea water and the mussel Protothaca jedoensis, have been characterized. Based on sequencing of the 16S rRNA gene, KMM 3299T showed the highest similarity (93-95%) to members of the genus Shewanella. The G+C contents of the DNAs of these strains were 43-44 mol%. The level of DNA homology between the two strains was conspecific (95%), indicating that they represent a distinct genospecies. These organisms were non-pigmented, Gram-negative, polarly flagellated, facultatively anaerobic, mesophilic, neutrophilic and able to degrade a wide range of high molecular mass polymers, including alginate, carrageenan, laminaran and agar. The novel organisms were susceptible to gentamycin, carbenicillin, lincomycin and oleandomycin. The predominant cellular fatty acids were i-15:0, 16:0, 16:1(n-7), 18:1(n-7). Eicosapentaenoic acid, 20:5(n-3), was detected in the two isolates at levels of 1-8%, depending on the temperature of cultivation. Phylogenetic evidence, together with phenotypic characteristics, showed that the two isolates studied constitute a novel species of the genus Shewanella. The name Shewanella japonica is proposed; the type strain is KMM 3299T(= LMG 19691T = CIP 106860T).

Animals↗
PubMed2002

Plasmid-borne macrolide resistance in Micrococcus luteus.

A plasmid designated pMEC2 which confers resistance to erythromycin, other macrolides, and lincomycin was detected in Micrococcus luteus strain MAW843 isolated from human skin. Curing of this approximately 4.2 kb plasmid from the host organism resulted in erythromycin sensitivity of the strain. Introduction of pMEC2 into a different M. luteus strain conferred erythromycin resistance upon this strain. Macrolide resistance in M. luteus MAW843 was an inducible trait. Induction occurred at subinhibitory erythromycin concentrations of about 0.02-0.05 micro g ml(-1). Erythromycin and oleandomycin were inducers, while spiramycin and tylosin exerted no significant inducer properties. With heterologous expression experiments in Corynebacterium glutamicum, using hybrid plasmid constructs and deletion derivatives thereof, it was possible to narrow down the location of the plasmid-borne erythromycin-resistance determinant to a region of about 1.8 kb of pMEC2. Sequence analysis of the genetic determinant, designated erm(36), identified an ORF putatively encoding a 281-residue protein with similarity to 23S rRNA adenine N(6)-methyltransferases. erm(36) was most related (about 52-54% identity) to erythromycin-resistance proteins found in high-G+C Gram-positive bacteria, including the (opportunistic) pathogenic corynebacteria Corynebacterium jeikeium, C. striatum, C. diphtheriae and Propionibacterium acnes. This is believed to be the first report of a plasmid-borne, inducible antibiotic resistance in micrococci. The possible role of non-pathogenic, saprophytic micrococci bearing antibiotic-resistance genes in the spreading of these determinants is discussed.

Anti-Bacterial Agents↗