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

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.


Introduction
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].
Sulfonamides are synthetic antibacterial drugs presenting a para-amino benzoic acid (PABA) structure and containing a sulfonamide group linked to an aromatic group that competitively inhibits the enzyme dihydropteroate synthase (DHPS). DHPS participates in folate synthesis, an essential mechanism for bacterial DNA and RNA synthesis, using PABA as a substrate, and this competitive inhibition of DHPS by sulfonamides inhibits bacterial growth [7][8][9][10]. Consequently, these drugs have activity against a broad spectrum of bacteria, being able to inhibit both Gram-negative and Gram-positive bacteria that do not possess mechanisms to overcome the inhibition effects of DHPS [11].
Sulfonamides were the first drugs to be used in veterinary medicine in therapeutic doses [12,13]. Their excessive usage imposed widespread selective pressures on bacteria, as seen by the high prevalence rates of sulfonamide resistance observed in mainly Gram-negative bacteria isolated from animals and humans all over the world in the past decade [14][15][16][17]. Another concern is the accumulation of sulfonamides as environmental

Search Strategy
The bibliographic search was conducted through the Virtual Health Library (VHL), a portal where bibliographic reference databases and full texts are available to search for physical and digital books, booklets, manuals, magazines, and legislation, among other services. VHL also accesses international databases such as Medline and Lilacs, among others. Publications relating antimicrobial resistance genes for Salmonella spp. were screened using the following terms: "tetracycline resistance genes", "sulfonamide resistance genes" and "Salmonella". The retrieved publications were selected to be studied.

Filters, Inclusion and Exclusion Criteria
According to the research interest, the terms were searched in the database from 2009 to 2019. The inclusion criteria were as follows: (1) the type of sample studied must have been reported; (2) the resistance genes sought; (3) the primers used in the polymerase chain reaction (PCR); and (4) thermocycler and PCR conditions. Studies were excluded if: (1) they had sought the resistance gene but did not present the primer sequence used in PCR; (2) the resistance gene was not towards tetracycline or sulfonamide; and (3) they did not have the thermocycler conditions used in PCR.

Data Extraction
Data were extracted from eligible studies according to the research criteria. For each study, the following characteristics were collected: the authors, the title of the study, the year of publication, the type of sample studied, the sample size, the resistance gene, the primers sequence of the genes, the thermocycler and PCR conditions, as well as the results.

Results and Discussion
Prevalence of tetracycline and sulfonamide resistant Salmonella spp. strains and distribution of tetracycline and sulfonamide resistance genes.
The search for articles associated with tetracycline and/or sulfonamide resistance genes to Salmonella spp. resulted in 25 studies that met the inclusion criteria (presented tetracycline and/or sulfonamide resistance genes, presented the primer sequence used in PCR and specified the thermocycler conditions used in PCR). Of the 25 studies, 6 searched for tet genes, 3 searched for sul genes, and 16 searched for both tet and sul genes. The general characteristics of the studies included in this review are summarized in Table 1. The percentage of tetracycline-resistant Salmonella spp. strains in relation to the total of Salmonella strains isolated in the studies varied from 25 to 100% (average of tetracyclineresistant isolates = 71.1%) ( Table 2). Similarly, Mąka et al. [28] reported tetracycline resistance frequencies among Salmonella spp. strains isolated from various meats (pork, chicken, turkey, beef, and fish) were often 50.0% or higher (50-76%) in Brazil, Canada, Iran, India, Turkey, UK and Vietnam. A high frequency of Salmonella bacteria showed resistance to tetracycline (62-69%) in some studies [60][61][62]. Romero-Barrios et al. [63] isolated 1495 Salmonella strains in raw chicken products processed in slaughterhouses inspected by the Canadian federal government and sold at retail, and of these 642 (42.9%) strains showed resistance to tetracycline. Lopes et al. [52] isolated a total of 225 Salmonella strains from feed, pigs, and carcasses in Brazil and resistance was found most frequently to tetracycline (54.5%). Wang et al. [64] analyzed a total of 11.447 isolates of S. Typhimurium recovered from humans (n = 6381), animals (n = 2940), and retail meats (n = 2126), and tetracycline resistance was around 70% for Salmonella strains isolated from animals and meats, and around 40% for strains of human origin.
For sulfonamide, the percentage of resistant isolates in relation to the total of Salmonella strains in the studies varied from 5.2 to 100% (average of sulfonamide-resistant isolates = 57.4%) ( Table 2). Other studies also reported high sulfonamide resistance in Salmonella strains [65][66][67][68][69]. Xu et al. [65] showed high Salmonella resistance to sulfonamide (73.0%) in the results for antimicrobial resistance profiles of strains isolated from chicken in China. Moe et al. [66] studied the antimicrobial resistance of Salmonella isolated from chicken carcasses in Myanmar and the isolates were most frequently resistant to trimethoprim-sulfamethoxazole (70.3%) and tetracycline (54.3%).
Sodagari et al. [68] studied the antimicrobial resistance of Salmonella serotypes isolated from retail chicken meat in Iran and found high antimicrobial resistance rates were against tetracycline (81%) and sulfamethoxazole-trimethoprim (61.2%). Zeng et al. [69] determined the antimicrobial resistance of Salmonella in pork, chicken, and duck from retail markets in China, and the highest resistance was to trimethoprim-sulfamethoxazole (94.5%), followed by tetracycline (55.4%).
Voss-Rech et al. [70] conducted a meta-analysis to assess the profile and temporal evolution of the antimicrobial resistance of nontyphoidal Salmonella isolated from poultry and humans in Brazil from 1995 to 2014. In the nontyphoidal isolates of poultry origin, the highest levels of antimicrobial resistance were verified for sulfonamides (44.3%), nalidixic acid (42.5%), and tetracycline (35.5%). In the human-origin isolates, the resistance occurred mainly for sulfonamides (46.4%), tetracycline (36.9%), and ampicillin (23.6%). Vaez et al. [71] also conducted a meta-analysis to determine the antimicrobial resistance profiles of Salmonella serotypes isolated from animals in Iran and isolates were mostly resistant against nalidixic acid (67%), then tetracycline (66.9%), followed by trimethoprim/sulfamethoxazole (41.6%).
The most searched tetracycline-resistance genes were: tetA with 21 studies (94.5%), tetB with 19 studies (86.4%), tetC with 11 studies (50.0%) and tetG with 10 studies (45.5%), while the least searched genes were tetD with 3 studies (13.6%) and tetE with 2 studies (9.1%) ( Figure 1). The tetA gene was found in all 21 studies that searched for this gene, and its presence in Salmonella spp. strains varied from 8.0 to 87.5% (average of tetA gene in isolates = 47.7%). The tetB gene was found in 12 studies and its presence in Salmonella spp. strains varied from 0 to 75.0% (average of tetB gene in isolates = 28.3%). The tetC gene was present in 6 studies and its presence in Salmonella spp. strains varied from 0 to 86.6% (average of tetC gene in isolates = 19.9%). The tetG gene was found in 9 studies and its presence in Salmonella spp. strains varied from 0 to 26.0% (average of tetG gene in isolates = 8.4%). The tetE and tetD genes were not present in Salmonella spp. isolates (Table 3). Salmonella strains isolated from animals and meats, and around 40% for strains of human origin. For sulfonamide, the percentage of resistant isolates in relation to the total of Salmonella strains in the studies varied from 5.2 to 100% (average of sulfonamide-resistant isolates = 57.4%) ( Table 2). Other studies also reported high sulfonamide resistance in Salmonella strains [65][66][67][68][69]. Xu et al. [65] showed high Salmonella resistance to sulfonamide (73.0%) in the results for antimicrobial resistance profiles of strains isolated from chicken in China. Moe et al. [66] studied the antimicrobial resistance of Salmonella isolated from chicken carcasses in Myanmar and the isolates were most frequently resistant to trimethoprim-sulfamethoxazole (70.3%) and tetracycline (54.3%).
Sodagari et al. [68] studied the antimicrobial resistance of Salmonella serotypes isolated from retail chicken meat in Iran and found high antimicrobial resistance rates were against tetracycline (81%) and sulfamethoxazole-trimethoprim (61.2%). Zeng et al. [69] determined the antimicrobial resistance of Salmonella in pork, chicken, and duck from retail markets in China, and the highest resistance was to trimethoprim-sulfamethoxazole (94.5%), followed by tetracycline (55.4%).
Voss-Rech et al. [70] conducted a meta-analysis to assess the profile and temporal evolution of the antimicrobial resistance of nontyphoidal Salmonella isolated from poultry and humans in Brazil from 1995 to 2014. In the nontyphoidal isolates of poultry origin, the highest levels of antimicrobial resistance were verified for sulfonamides (44.3%), nalidixic acid (42.5%), and tetracycline (35.5%). In the human-origin isolates, the resistance occurred mainly for sulfonamides (46.4%), tetracycline (36.9%), and ampicillin (23.6%). Vaez et al. [71] also conducted a meta-analysis to determine the antimicrobial resistance profiles of Salmonella serotypes isolated from animals in Iran and isolates were mostly resistant against nalidixic acid (67%), then tetracycline (66.9%), followed by trimethoprim/sulfamethoxazole (41.6%).
The most searched tetracycline-resistance genes were: tetA with 21 studies (94.5%), tetB with 19 studies (86.4%), tetC with 11 studies (50.0%) and tetG with 10 studies (45.5%), while the least searched genes were tetD with 3 studies (13.6%) and tetE with 2 studies (9.1%) ( Figure 1). The tetA gene was found in all 21 studies that searched for this gene, and its presence in Salmonella spp. strains varied from 8.0 to 87.5% (average of tetA gene in isolates = 47.7%). The tetB gene was found in 12 studies and its presence in Salmonella spp. strains varied from 0 to 75.0% (average of tetB gene in isolates = 28.3%). The tetC gene was present in 6 studies and its presence in Salmonella spp. strains varied from 0 to 86.6% (average of tetC gene in isolates = 19.9%). The tetG gene was found in 9 studies and its presence in Salmonella spp. strains varied from 0 to 26.0% (average of tetG gene in isolates = 8.4%). The tetE and tetD genes were not present in Salmonella spp. isolates (Table 3).    Zhang et al. [72] reported that among 105 tetracycline-resistant Salmonella, tetA gene was most frequently detected (80.9%), and only 4.8% of isolates harbored tetB gene. The authors [73] reported that tetA and tetB genes are widely detected in fecal coliforms from rivers and animal sources. Matielo et al. [73] determined the antimicrobial resistance in Salmonella enterica strains isolated from Brazilian poultry production, and the genes tetA, tetB and tetC were detected in 60%, 5% and 5% of these isolates, respectively. Sanchez-Maldonado et al. [74] searched the antimicrobial resistance of Salmonella isolated from two pork processing plants in Canada, and the most prevalent genes were tetB, found in 21.3% of isolates and tetA, found in 12.6% of isolates.
According to Roberts and Schwarz [25], the tetB gene is specific for Gram-negative aerobic and facultative anaerobic bacteria, being present in 33 Gram-negative genera. If other aerobic and facultative anaerobic Gram-negative genes are of interest, the tetA gene is the next most common, being present in 23 Gram-negative genera. The tet genes are the most regularly found in Enterobacteriaceae [61]. The most common tetracycline resistance mechanism is antibiotic efflux pumps, in which tet genes encode the membrane-associated efflux proteins, which exchange a proton for a tetracycline-cation complex against a concentration gradient, exporting the drug to outside bacterial cells. These genes are generally associated with plasmids, transposons, or both and are often conjugative [2,3,28].
Tet genes belong to classes A, B, C, D and G are placed in the same group due to amino acid sequence similarity. The tetracycline resistance proteins in this group have from 41% to 78% amino acid identity [75]. Efflux of tetracyclines predominantly occurs via proteins that are members of the major facilitator superfamily group of integral membrane transporters. These efflux pumps are integral membrane proteins that span the lipid bilayer of the inner cell membrane. Based on homology to other known transporters, the membrane-spanning regions of the protein are predicted to be helical. The structure-function predicts a waterfilled channel surrounded by six transmembrane helices. The tetracycline is predicted to pass through this channel and is exchanged for H + . It is this vectorial flow of protons through the channel, down the pH gradient, which provides the energy required to pump the antibiotic from the cell [76].
The most searched sulfonamide-resistance genes were: sul1 with 19 studies (82.6%), sul2 with 13 studies (56.5%), while the least searched genes were sul3 with 7 studies (30.4%), and sul4 with 1 study (4.3%) (Figure 2). The sul1 gene was found in 18 of 19 studies that searched for this gene, and its presence in Salmonella spp. strains varied from 0 to 89.7% (average of sul1 gene in isolates = 45.6%). The sul2 gene was found in 12 studies and its presence in Salmonella spp. strains varied from 0 to 97.8% (average of sul2 gene in isolates = 44.5%). The sul3 gene was found in six studies and its presence in Salmonella spp. strains varied from 0 to 85.1% (average of sul3 gene in isolates = 31.6%) ( Table 3). is the next most common, being present in 23 Gram-negative genera. The tet genes are the most regularly found in Enterobacteriaceae [61]. The most common tetracycline resistance mechanism is antibiotic efflux pumps, in which tet genes encode the membrane-associated efflux proteins, which exchange a proton for a tetracycline-cation complex against a concentration gradient, exporting the drug to outside bacterial cells. These genes are generally associated with plasmids, transposons, or both and are often conjugative [2,3,28].
Tet genes belong to classes A, B, C, D and G are placed in the same group due to amino acid sequence similarity. The tetracycline resistance proteins in this group have from 41% to 78% amino acid identity [75]. Efflux of tetracyclines predominantly occurs via proteins that are members of the major facilitator superfamily group of integral membrane transporters. These efflux pumps are integral membrane proteins that span the lipid bilayer of the inner cell membrane. Based on homology to other known transporters, the membrane-spanning regions of the protein are predicted to be helical. The structurefunction predicts a water-filled channel surrounded by six transmembrane helices. The tetracycline is predicted to pass through this channel and is exchanged for H + . It is this vectorial flow of protons through the channel, down the pH gradient, which provides the energy required to pump the antibiotic from the cell [76].
The most searched sulfonamide-resistance genes were: sul1 with 19 studies (82.6%), sul2 with 13 studies (56.5%), while the least searched genes were sul3 with 7 studies (30.4%), and sul4 with 1 study (4.3%) (Figure 2). The sul1 gene was found in 18 of 19 studies that searched for this gene, and its presence in Salmonella spp. strains varied from 0 to 89.7% (average of sul1 gene in isolates = 45.6%). The sul2 gene was found in 12 studies and its presence in Salmonella spp. strains varied from 0 to 97.8% (average of sul2 gene in isolates = 44.5%). The sul3 gene was found in six studies and its presence in Salmonella spp. strains varied from 0 to 85.1% (average of sul3 gene in isolates = 31.6%) ( Table 3). Ma et al. [77] determined the antimicrobial resistance of Salmonella isolated from chickens and pigs on farms, abattoirs, and markets in Sichuan Province, China and among 74 strains carrying sulfonamides resistance gene, sul1 was the most common (43.2%), followed by sul2 (55.4%) and sul3 (25.7%). Sanchez-Maldonado et al. [74] searched the antimicrobial resistance of Salmonella isolated from two pork processing plants in Alberta, Canada, and the most prevalent genes among those screened were sul2, found in 21.3% of isolates and sul1, found 18.1% of isolates. Zhu et al. [59] reported that the presence of the Ma et al. [77] determined the antimicrobial resistance of Salmonella isolated from chickens and pigs on farms, abattoirs, and markets in Sichuan Province, China and among 74 strains carrying sulfonamides resistance gene, sul1 was the most common (43.2%), followed by sul2 (55.4%) and sul3 (25.7%). Sanchez-Maldonado et al. [74] searched the antimicrobial resistance of Salmonella isolated from two pork processing plants in Alberta, Canada, and the most prevalent genes among those screened were sul2, found in 21.3% of isolates and sul1, found 18.1% of isolates. Zhu et al. [59] reported that the presence of the genes sul1 and sul2 was equal in Salmonella strains isolated from pork meat resistant to trimethoprim/sulfamethoxazole in China.
Zhu et al. [43] reported that among 91 sulfonamide-resistant isolates, 97.8% (n = 89) harbored at least one of the genes studied (sul1, sul2 or sul3). The sul2 gene had the highest occurrence (97.8%, n = 89) compared to the sul1 and sul3 genes (both with 50.5%, n = 46). According to Mąka et al. [7] dissemination of sul1 and sul2 genes among Salmonella spp. is reported more often than sul3 gene. Xu et al. [10] also reported that sul1 and sul2 genes are often found at roughly the same frequency among sulfonamide resistant Gram-negative isolates. According to Machado et al. [78] the presence of sul genes continues to be reported in surveys of environmental bacteria with sul2 dominating but closely followed by sul1, and sul3 is still rarer.
The sul genes are found in plasmids and are associated with ubiquitous and longknown sulfonamide resistance Gram-negative bacteria [10]. The sul1 gene is typically found in class 1 integrons and linked to other resistance genes, whereas sul2 gene is usually associated with small multicopy plasmids or large transmissible multiresistance plasmids [8,19]. The sul3 gene was identified in conjugative plasmids in E. coli, while the sul4 gene was identified in a systematic prospection of class 1 integron genes in Indian river sediments [8].
According to Perreten and Boerlin [31] sul1 and sul2 from E. coli share 57% of DNA identity and sul3 revealed amino acid identities of 50.4% overall to sul2 from Salmonella enterica subsp. enterica plasmid, and 40.9% to sul1 from E. coli plasmid. Based on amino acid homology and phenotype, sul3 was considered a new sulfonamide-resistant DHPS. According to Razavi et al. [32] sul4 was identified with 31-33% identity to known mobile sulfonamide resistance genes (sul1, sul2 and sul3). Based on its ability to provide sulfonamide resistance, its mobile character, as demonstrated by its presence in integrons, and the homology to previously known sulfonamide resistance genes, the name sul4 was proposed. Structural prediction of sul1, sul2, sul3 and sul4 indicates strong overall similarities. The structure of the genes contains the binding sites for 7,8-dihydropterin pyrophosphate (DHPP), para-aminobenzoic acid (PABA), and sulfonamide. After DHPP has bound deep in the structure, sulfonamide binds near the surface of the protein. Thus, sulfonamide binding is affected by changes near the surface of DHPS [32].
The genes sul1, sul2, sul3 and sul4 can spread among bacteria of the same or different species by conjugation or transformation, thereby disseminating resistance genes [10,19]. Some studies about sulfonamide resistant isolates where none of these sul genes are detected have appeared in the literature, but so far, no other plasmid sulfonamide resistance gene has been reported [78,79].
Deekshit et al. [80] found that the tetA gene in strains of Salmonella spp. isolated from seafood in India was located on a plasmid and this gene was identical to tetA detected in other bacterial species including Escherichia coli and Vibrio cholerae. According to Vital et al. [41], large conjugative resistance plasmids have been detected in Salmonella food isolates from several countries. Conjugative plasmids can transfer several resistance genes between different bacterial species, and the presence of multiple antibiotic resistance genes facilitates their host survival despite intense antibiotic selection [25].
Selected tet genes are part of multiresistance elements, such as the integrative and mobilizable Salmonella genomic island 1. The majority of the tetracycline-resistance efflux genes have been linked to other antibiotic-resistance genes. These tet genes have been identified in environmental, animal and aquaculture-associated bacteria [81]. Hsu et al. [48] reported that high rates of bacterial resistance to antibiotics such as tetracycline are associated with the intensive use of these drugs in veterinary medicine. Hence, the emergence of resistant bacteria in the food chain has been a cause of great concern, even with the decline of tetracyclines use in clinical treatment [82,83].
Adesiji et al. [84] detected tet-resistant genes in tet-susceptible Salmonella isolates. The results show that some antimicrobial-resistant genes are silent in bacteria in vitro and indicate that these silent genes can turn on in vivo under selective antibiotic pressure or spread to other bacteria. These results reinforce the importance of determining tet and sul genes in addition to antimicrobial susceptibility tests. Wang et al. [85] also reported some silent or unexpressed sul1 and sul3 genes detected in the isolates of soils, which could be horizontally transferred or expressed under other conditions. Table 4 presents the primer sequences and PCR conditions used to amplify resistance genes in the studies. The primer sequences used to amplify tetracycline and sulfonamide resistance genes in the studies were a vital inclusion criterion, as designing appropriate primers is essential to a successful PCR experiment outcome [86].

Authors Genes Searched Primers PCR Amplification Conditions
Lopes et al. [52] tetA F: GTAATTCTGAGCACTGT R: CCTGGACAACATTGCTT Initial denaturation at 94 • C for 4 min, followed by 34 cycles of denaturation at 94 • C for 1 min, annealing at 43 • C for 2 min, and extension at 72 • C for 3 min, with an additional extension at 72 • C for 7 min.     The target specificity is a critical primer property, and, ideally, a primer pair should only amplify the intended target. Several software tools have been developed to aid the primer design process. The Primer3 program is widely used in designs of the primers, however, it does not analyze the target of the primers specificity, so the user will need additional tools such as the software Primer-BLAST to test for specificity. This software ensures a complete primer-target alignment while being sensitive enough to detect a significant number of primer-target mismatches. Primer-BLAST software can also help design new target-specific primers in one step and check pre-existing specificity of the primers [87].
Another essential factor for the success of the experiment is the optimization of the conditions of the PCR. The choice of the correct thermal cycling conditions is vital to obtain better results in the research and replication of the method. In addition to bringing efficient results and reducing the attempts of the researcher, the optimization of PCR conditions also avoids some common problems, such as the amplifying of non-specific products or the absence of a product in the result [88].
The most frequent samples used in studies to isolate Salmonella spp. strains were: 13 samples from poultry-origin (52.0%), followed by 11 samples from swine-origin (44.0%) and 7 samples from bovine-origin (28.0%); while 4 studies used human samples, 2 studies used goat samples, 2 studies used water samples, 1 study used hen eggs, and another study used fresh vegetable samples (Table 5).
Salmonellosis is a significant zoonosis worldwide and is widespread in animals [89,90]. The present review found that the most frequent Salmonella isolates were from poultry and pork meat samples. Chicken meat is a widely consumed product worldwide, and different studies register contamination by Salmonella in this type of food [27,42,43]. Ren et al. [91] reported that the high contamination rates in the supply chain show that chicken products are an important vector of S. enterica. Previous studies have shown that the continuous circulation of S. enterica in the broiler supply system poses a potential risk of spreading Salmonella to humans [91][92][93][94][95].
Salmonella contamination in poultry and pigs is often asymptomatic and rarely causes less severe and transient diarrhea. Consumption of contaminated chicken and pork predisposes humans to Salmonella infection [42,43,96]. The presence of Salmonella in cattle in some studies [38,40,55] and the possibility of cross-contamination of the carcass in the slaughter of these animals may pose a risk to food safety in the consumption of this type of food [97].
Salmonella ssp. is an etiologic agent often cited as causing foodborne diseases [98,99]. In most cases, salmonellosis is caused by contaminated food products, particularly of animal origins such as poultry, eggs, beef, and pork [44]. The genetic constitution of these bacteria allows them to adapt to various environments and animals, including mammalian and non-mammalian hosts, making them widespread worldwide [82].
The abusive use of tetracycline and sulfonamides associated with the presence of Salmonella in different food sources has promoted the rise of resistant strains [42,81,99]. In Brazil, despite the ban on the use of antibiotics as performance enhancers in poultry production [100], tetracyclines have already been widely used as growth promoters. The presence of resistance genes found in this review suggests a remarkable ability of Salmonella spp. to survive in environments where antimicrobial agents are broadly used [42].
There is further concern regarding the release of these substances into the environment through hospital and industrial effluents, domestic sewage, and the disposal of expired drugs. Additionally, any resistance in potentially virulent strains of humans and animals can quickly spread, making their circulation in the environment more frequent [101][102][103][104][105].

Conclusions
The results obtained in this study revealed that the tetracycline resistance genes most frequently isolated from Salmonella spp. were tetA and tetB. The genes sul1 and sul2 were the most frequently sulfonamide-resistant genes present in Salmonella. The chicken and pork samples presented the most significant number of these resistance genes. The intensive use of tetracycline and sulfonamides antibiotics in the production chain of these foods must have resulted in the development of this resistance. Bacterial resistance represents a significant public health concern, as there is a possibility of transferring resistance genes between humans, animals, and the environment.