Genetic basis of macrolide and lincosamide resistance inBrachyspira(Serpulina)hyodysenteriae

Karlsson, Märit; Fellström, Claes; Heldtander, M.; Johansson, Karl‐Erik; Franklin, A.

doi:10.1111/j.1574-6968.1999.tb13476.x

Cited by 90 publications

(28 citation statements)

References 21 publications

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“…Cross-resistance between macrolides and lincosamides can be observed because they share a target site for drug binding (36). A single mutation in one position of the 23S rRNA gene of B. hyodysenteriae and B. pilosicoli is sufficient to cause resistance to both tylosin and lincomycin, and a previous study demonstrated rapid in vitro development of the causative mutation in the 23S rRNA gene of B. hyodysenteriae (36,37). Rapid development of resistance followed by multiplication and transmission of such strains can lead to widespread tylosin and lincomycin resistance within a population.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated from Swine Herds in the United States

2016

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Outbreaks of swine dysentery, caused by Brachyspira hyodysenteriae and the recently discovered "Brachyspira hampsonii," have reoccurred in North American swine herds since the late 2000s. Additionally, multiple Brachyspira species have been increasingly isolated by North American diagnostic laboratories. In Europe, the reliance on antimicrobial therapy for control of swine dysentery has been followed by reports of antimicrobial resistance over time. The objectives of our study were to determine the antimicrobial susceptibility trends of four Brachyspira species originating from U.S. swine herds and to investigate their associations with the bacterial species, genotypes, and epidemiological origins of the isolates. We evaluated the susceptibility of B. hyodysenteriae, B. hampsonii, Brachyspira pilosicoli, and Brachyspira murdochii to tiamulin, valnemulin, doxycycline, lincomycin, and tylosin by broth microdilution and that to carbadox by agar dilution. In general, Brachyspira species showed high susceptibility to tiamulin, valnemulin, and carbadox, heterogeneous susceptibility to doxycycline, and low susceptibility to lincomycin and tylosin. A trend of decreasing antimicrobial susceptibility by species was observed (B. hampsonii > B. hyodysenteriae > B. murdochii > B. pilosicoli). In general, Brachyspira isolates from the United States were more susceptible to these antimicrobials than were isolates from other countries. Decreased antimicrobial susceptibility was associated with the genotype, stage of production, and production system from which the isolate originated, which highlights the roles of biosecurity and husbandry in disease prevention and control. Finally, this study also highlights the urgent need for Clinical and Laboratory Standards Institute-approved clinical breakpoints for Brachyspira species, to facilitate informed therapeutic and control strategies.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated from Swine Herds in the United States

2016

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“…Tylosin is sometimes used to treat mycoplasma infections in poultry, and it is possible that such exposure in the Queensland and non-Australian flocks had encouraged the development of resistance. The generally low levels of susceptibility to tylosin among the chicken isolates, and an associated tendency for these also to have elevated MIC ranges to lincomycin, mirrors the situation seen among porcine isolates of B. hyodysenteriae and B. pilosicoli (Karlsson et al ., 2002(Karlsson et al ., , 2004. Currently it is not known whether this resistance in the chicken isolates was caused by the common point mutations in the 23S rRNA described as being responsible for macrolide and lincosamide resistance among porcine isolates of B. hyodysenteriae and B. pilosicoli (Karlsson et al , 1999(Karlsson et al , , 2004.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that isolates of B. hyodysenteriae and B. pilosicoli that infect pigs may develop resistance if regularly exposed to antimicrobials (Karlsson et al ., 2002(Karlsson et al ., , 2004, and the same is likely to be true for Brachyspira spp. isolates from chickens.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial susceptibility testing ofBrachyspira intermediaandBrachyspira pilosicoliisolates from Australian chickens

2006

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Susceptibilities of predominantly Australian isolates of the pathogenic intestinal spirochaetes Brachyspira intermedia (n0/25) and Brachyspira pilosicoli (n 0/17) from chickens were tested in agar dilution against four concentrations each of the antimicrobials tiamulin, lincomycin, tylosin, metronidazole, tetracycline and ampicillin. Based on available minimum inhibitory concentration (MIC) breakpoint values for Brachyspira hyodysenteriae or other Gram-negative enteric veterinary pathogens, isolates of both species generally were susceptible to tiamulin, lincomycin, metronidazole and tetracycline. Although not classed as resistant, four isolates of B. intermedia had an elevated MIC range for tiamulin (1 to 4 mg/l), 11 isolates of B. intermedia and five of B. pilosicoli had an elevated MIC range for lincomycin (10 to 50 mg/l), one isolate of B. pilosicoli had an elevated MIC range for tetracycline (10 to 20 mg/l), and one isolate of B. intermedia and five of B. pilosicoli had an elevated MIC range for ampicillin (10 to 50 mg/l). A clear lack of susceptibility to tylosin

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“…12 and 13). Mutations in 23S rRNA conferring macrolide resistance have been described for clinical strains of Mycobacterium intracellulare (14), Mycobacterium avium (15,16), Mycobacterium kansasii (17), Mycobacterium chelonae, Mycobacterium abscessus (18), Helicobacter pylori (19)(20)(21), Brachyspira (Serpulina) hyodysenteriae (22), Propionibacterium spp. (23), and Streptococcus pneumoniae (24).…”

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23S rRNA base pair 2057–2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A→G

Pfister

Corti

Hobbie

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations.antibiotics ͉ ketolides ͉ ribosomes ͉ structure ͉ conformation M any groups of clinically useful antibiotics prevent the synthesis of new proteins by interacting with the bacterial ribosome (1). A prominent region targeted by ribosomal drugs is located around the peptide bond formation site (the peptidyl transferase center) and the entrance of the nascent protein exit tunnel on the large (50S) ribosomal subunit. The upper region of the tunnel provides the binding site for macrolide, lincosamide, and streptogramin B (MLS B ) antibiotics (2-6). The primary inhibitory effect of the lincosamide drugs is to inhibit the formation of peptide bonds; the main inhibitory effect of macrolides is to block the passage of the newly synthesized peptide chain through the exit tunnel (2).Macrolides have a common core structure formed by a lactone ring of different sizes (7). Ketolides are the latest derivatives developed from the macrolide erythromycin to improve antimicrobial activity. They are equipped with 3-keto and 6-methoxy groups that improve acid stability and allow drug binding without evoking resistance mediated by inducible erm genes (reviewed in ref. 8). Additional features are a cyclic carbamate at C11͞C12 and an extended arm that provides additional interactions with domain II of 23S rRNA (4, 5, 9-11): an alkyl-aryl extension bound to the cyclic carbamate in the case of telithromycin and a quinolylallyl group tethered to the O-6 position in the case of ABT-773.Resistance to macrolides occurs predominantly by modification of the drug-binding site and͞or by drug efflux. Target modification may be the result of two different mechanisms: (i) modification in trans conferred by erm genes, which methylate the adenine of 23S rRNA position 2058 and (ii) modification in cis, including mutational altera...

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Genetic basis of macrolide and lincosamide resistance inBrachyspira(Serpulina)hyodysenteriae

Cited by 90 publications

References 21 publications

Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated from Swine Herds in the United States

Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated from Swine Herds in the United States

Antimicrobial susceptibility testing ofBrachyspira intermediaandBrachyspira pilosicoliisolates from Australian chickens

23S rRNA base pair 2057–2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A→G

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