An overview of tetracyclines and related resistance mechanisms

Campylobacter spp. are among the leading foodborne pathogens, causing campylobacteriosis, a zoonotic infection that results in bacterial gastroenteritis and diarrheal disease in animals and humans. This study investigated the molecular epidemiology of antibiotic-resistant Campylobacter spp. isolated across the farm-to-fork-continuum in an intensive pig production system in South Africa. Following ethical approval, samples were collected over sixteen weeks from selected critical points (farm, transport, abattoir, and retail) using a farm-to-fork sampling approach according to WHO-AGISAR guidelines. Overall, 520 samples were investigated for the presence of Campylobacter spp., which were putatively identified using selective media with identity and speciation confirmed by polymerase chain reaction (PCR) of specific genes. Resistance profiles were ascertained by the Kirby–Bauer disk diffusion method. Antibiotic resistance and virulence genes were identified using PCR and DNA sequencing. Clonal relatedness was determined using ERIC-PCR. Altogether, 378/520 (72.7%) samples were positive for Campylobacter spp., with Campylobacter coli being the predominant species (73.3%), followed by Campylobacter jejuni (17.7%); 8.9% of the isolates were classified as “other spp”. Relatively high resistance was observed in C. coli and C. jejuni to erythromycin (89% and 99%), streptomycin (87% and 93%), tetracycline (82% and 96%), ampicillin (69% and 85%), and ciprofloxacin (53% and 67%), respectively. Multidrug resistance (MDR) was noted in 330 of the 378 (87.3%) isolates. The antibiotic resistance genes observed were tetO (74.6%), blaOXA-61 (2.9%), and cmeB (11.1%), accounting for the resistance to tetracycline and ampicillin. The membrane efflux pump (cmeB), conferring resistance to multiple antibiotics, was also detected in most resistant isolates. Chromosomal mutations in gyrA (Thr-86-Ile) and 23S rRNA (A2075G and A2074C) genes, conferring quinolone and erythromycin resistance, respectively, were also found. Of the virulence genes tested, ciaB, dnaJ, pldA, cdtA, cdtB, cdtC, and cadF were detected in 48.6%, 61.1%, 17.4%, 67.4%, 19.3%, 51%, and 5% of all Campylobacter isolates, respectively. Clonal analysis revealed that isolates along the continuum were highly diverse, with isolates from the same sampling points belonging to the same major ERIC-types. The study showed relatively high resistance to antibiotics commonly used in intensive pig production in South Africa with some evidence, albeit minimal, of transmission across the farm-to-fork continuum. This, together with the virulence profiles present in Campylobacter spp., presents a challenge to food safety and a potential risk to human health, necessitating routine surveillance, antibiotic stewardship, and comprehensive biosecurity in intensive pig production.

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“…from intensive food animal production in KwaZulu-Natal. Nevertheless, the efflux genes, tetA and tetB , have also been reported [ 5 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Occurrence, Antimicrobial Resistance, and Molecular Characterization of Campylobacter spp. in Intensive Pig Production in South Africa

et al. 2021

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“…Tetracyclines are broad-spectrum antibacterial agents, which show activity against most Gram-positive and Gram-negative bacteria, both anaerobic and aerobic. The tetracyclines mode of action is well established; they inhibit bacterial protein synthesis by avoiding the association between RNA molecules and the 30S subunit of the bacterial ribosome, thus preventing the addition of amino acids and, consequently, protein synthesis [ 1 , 2 , 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…The growth-promoting properties of tetracyclines were first described in 1949 for chickens, and farmers widely used them in animal husbandry thanks to improvement of the growth rate to feed intake ratio [ 12 , 13 ]. This extensive use favored the emergence of tetracycline resistance in a diverse group of bacteria and caused restrictions on the clinical utility of these compounds [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Tetracycline resistance in most bacteria is due to the acquisition of mobile genetic elements, ribosomal binding site mutations and chromosomal mutations leading to increased expression of intrinsic resistance mechanisms. Three principal tetracycline resistance mechanisms are efflux pumps, ribosomal protection, and enzymatic inactivation of tetracyclines drugs [ 1 , 3 , 24 , 25 ]. Several different tet genes have been described as conferring resistance to tetracyclines in bacteria.…”

Section: Introductionmentioning

confidence: 99%

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Presence of Tetracycline and Sulfonamide Resistance Genes in Salmonella spp.: Literature Review

et al. 2021

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Tetracyclines and sulfonamides are broad-spectrum antibacterial agents which have been used to treat bacterial infections for over half a century. The widespread use of tetracyclines and sulfonamides led to the emergence of resistance in a diverse group of bacteria. This resistance can be studied by searching for resistance genes present in the bacteria responsible for different resistance mechanisms. Salmonella is one of the leading bacteria causing foodborne diseases worldwide, and its resistance to tetracyclines and sulfonamides has been widely reported. The literature review searched the Virtual Health Library for articles with specific data in the studied samples: the resistance genes found, the primers used in PCR, and the thermocycler conditions. The results revealed that Salmonella presented high rates of resistance to tetracycline and sulfonamide, and the most frequent samples used to isolate Salmonella were poultry and pork. The tetracycline resistance genes most frequently detected from Salmonella spp. were tetA followed by tetB. The gene sul1 followed by sul2 were the most frequently sulfonamide resistance genes present in Salmonella. These genes are associated with plasmids, transposons, or both, and are often conjugative, highlighting the transference potential of these genes to other bacteria, environments, animals, and humans.

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“…The resistance to tetracyclines is determined by several mechanisms that are supported by tetracycline resistance proteins known as Tet proteins. The most common tetracycline resistance mechanisms include an active efflux of drugs from the bacterial cell, ribosomal protection from drug action, and enzymatic inactivation of drugs [ 21 , 24 , 25 ]. Until now, 61 different tetracyclines resistance genes ( tet ) encoding Tet proteins, often associated with transposons or plasmids, have been characterized [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Trueperella pyogenes Isolates from Livestock and European Bison (Bison bonasus) as a Reservoir of Tetracycline Resistance Determinants

et al. 2021

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Determinants of tetracycline resistance in Trueperella pyogenes are still poorly known. In this study, resistance to tetracycline was investigated in 114 T. pyogenes isolates from livestock and European bison. Tetracycline minimum inhibitory concentration (MIC) was evaluated by a microdilution method, and tetracycline resistance genes were detected by PCR. To determine variants of tetW and their linkage with mobile elements, sequencing analysis was performed. Among the studied isolates, 43.0% were tetracycline resistant (MIC ≥ 8 µg/mL). The highest MIC90 of tetracycline (32 µg/mL) was noted in bovine and European bison isolates. The most prevalent determinant of tetracycline resistance was tetW (in 40.4% of isolates), while tetA(33) was detected only in 8.8% of isolates. Four variants of tetW (tetW-1, tetW-2, tetW-3, tetW-4) were recognized. The tetW-3 variant was the most frequent and was linked to the ATE-1 transposon. The tetW-2 variant, found in a swine isolate, was not previously reported in T. pyogenes. This is the first report on determinants of tetracycline resistance in T. pyogenes isolates from European bison. These findings highlight that wild animals, including wild ruminants not treated with antimicrobials, can be a reservoir of tetracycline-resistant bacteria carrying resistance determinants, which may be easily spread among pathogenic and environmental microorganisms.

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An overview of tetracyclines and related resistance mechanisms

Cited by 34 publications

References 65 publications

Occurrence, Antimicrobial Resistance, and Molecular Characterization of Campylobacter spp. in Intensive Pig Production in South Africa

Occurrence, Antimicrobial Resistance, and Molecular Characterization of Campylobacter spp. in Intensive Pig Production in South Africa

Presence of Tetracycline and Sulfonamide Resistance Genes in Salmonella spp.: Literature Review

Trueperella pyogenes Isolates from Livestock and European Bison (Bison bonasus) as a Reservoir of Tetracycline Resistance Determinants

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