‘Antibiotic resistance’ assesses the challenge of antibiotic resistance. The problem was perceived to be driven by the acute crisis in the continued capability to treat infections caused by Gram-negative bacteria. The simplest form of resistance is mutational, which is the reason why doses of antibiotic have to exceed a concentration threshold to prevent the mutants surviving (Mutant Prevention Concentration). Resistance genes can be imported en bloc by plasmids. Bacteria use major mechanisms of resistance to overcome antibiotics. It is also worth considering antiseptics and biocides, clinical resistance, the clonality of resistant bacteria, and resistance in animal bacteria.

The emergence of antibiotic-resistant bacteria has become a major threat to public health. The increased use of antibiotics has selected for the dissemination of antibiotic resistance genes between organisms from different species and different genera. There is a large body of evidence that the indigenous microbiota can act as a reservoir of antibiotic-resistant bacteria. However little is known about the molecular basis for this in bacteria from the oral cavity. Therefore the aim of this work was to determine the prevalence of antibiotic-resistant bacteria and antibiotic resistance genes in the cultivable oral microbiota. Saliva and plaque samples were taken from each of 60 healthy adults who had not taken any antibiotics during the previous three months. Each sample was plated onto antibiotic-containing media to quantitate and identify antibiotic-resistant strains. All of the individuals harboured bacteria resistant to erythromycin, gentamicin, vancomycin and tetracycline. Only 4 individuals (7%) did not have any cultivable bacteria resistant to amoxycillin. Oral bacteria resistant to gentamicin were the most commonly isolated (constituting 23% of total cultivable oral bacteria) followed by erythromycin (18% of the total viable count), vancomycin (16% of the total viable count), tetracycline (10% of the total viable count) and amoxycillin (4% of the total viable count). Multiply-resistant bacteria were found with 55% of tetracycline-resistant isolates being resistant also to erythromycin and 6% resistant also to both amoxycillin and erythromycin. The most prevalent genes encoding tetracycline and erythromycin resistance were tet(M), tet(W), tet(0), and mef and erm(B) respectively. In some cases, tet(M) and ermB were contained within a Tn/5 5-like conjugative transposon and could be co-tranferred to Enterococcus faecalis. Finally the nature of the genetic support for one of the tet(W) genes, was determined and found to be flanked by two transposases belonging to two different families of insertion sequences (IS30 and IS256). This element was highly unstable in E. coli. This study showed that antibiotic-resistant bacteria and antibiotic resistance genes are present in the oral microbiota and that oral bacteria are likely to play an important role in the evolution and dissemination of antibiotic resistance genes

Irrational antibiotic use contributes to the development of antibiotic resistance in bacteria, which is a major cause of healthcare-associated infections globally. Molecular research has shown that multiple resistance frequently develops from the uptake of pre-existing resistance genes, which are subsequently intensified under selective pressures. Resistant genes spread and are acquired through mobile genetic elements which are essential for facilitating horizontal gene transfer. MGEs have been identified as carriers of genetic material and are a significant player in evolutionary processes. These include insertion sequences, transposons, integrative and conjugative elements, plasmids, and genomic islands, all of which can transfer between and within DNA molecules. With an emphasis on pathogenic bacteria, this review highlights the salient features of the MGEs that contribute to the development and spread of antibiotic resistance. MGEs carry non-essential genes, including AMR and virulence genes, which can enhance the adaptability and fitness of their bacterial hosts. These elements employ evolutionary strategies to facilitate their replication and dissemination, thus enabling survival without positive selection for the harboring of beneficial genes.

Objectives: This study aimed to examine the relationships between isolated bacterial agents, age, and gender, as well as antibiotic resistance of UTI isolates, in addition to investigate the antibiotic resistance in a section of Iraqi patients with UTI. Methods: Isolates (885) from patients and outpatients with symptomatic urinary tract infections at Al-Sadder teaching hospital in Basra province, southern Iraq, from January to August 2022. Results: The results of patient specimens cultured on appropriate culture media indicate that the number of negative cultures was 528 while the number of positive cultures was 357; females are more susceptible to UTIs than males (170). The age category 60 years had the highest infection rate (31%), followed by 20-29 years (19.3%). The most prevalent etiological agent was Escherichia coli (28.3%), followed by Staphylococcus spp. (19.3%), Candida albicans (14.9%), and Klebsiella pneumonia (14.9%). Conclusion: The results demonstrate that various bacteria exhibit variable degrees of sensitivity to different antibiotics, with the significant finding that the majority of urinary isolates were highly resistant to commonly used antibiotics.

Abstract

Introduction- Antibiotic to treat dental caries infection are routinely prescribed. Bacteria have increased resistance to the currently recommended antibiotics. The purpose of this investigation was to perform antibiotic susceptibility on a panel pathogenic strain of bacteria isolated step by step from dental caries infection. 
Materials and Methods-Bacteria were isolated from caries site of patients and cultivated identified at the species level. Each of 150 species of bacteria was tested for antibiotics susceptibility to a five antibiotics using Etest. Antibiotic used were Amoxicillin, Cloxocillin, Erythromycin, Tetracycline, Penicillin-V.
Results- The percentages of Resistance in treatment for each antibiotic in this study were penicillin V: 72/150 (48%), Tetracycline: 99/150 (66%), amoxicillin: 135/150 (90%), Cloxocillin: 117/150 (78%), and Erythromycin: 90/150 (60%) (Table 1). If combination antibiotic therapy had been used to treat the bacteria isolated from dental caries, the percentage of Resistance for the combination of penicillin V/Amoxicillin would have been 39/150 (26%), and the combination of amoxicillin/ Erythromycin would have been 45/150 (30%).
Conclusion- This study demonstrated the Molecular Mechanism of antibiotic resistance and susceptibility pattern, of bacteria causing dental caries. The comprehensive results data obtained will allow in investigating spatial distribution of pathogenic antibiotic resistant bacteria in patients of dental caries. In turn this will allow the development of novel diagnostic and treatment methods. 
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Background: A global problem of multi-drug resistance (MDR) among bacteria is the cause of hundreds of thousands of deaths every year. In response to the significant increase of MDR bacteria, legislative measures have widely been taken to limit or eliminate the use of antibiotics, including in the form of feed additives for livestock, but also in metaphylaxis and its treatment, which was the subject of EU Regulation in 2019/6. Numerous studies have documented that bacteria use both phenotypis and gentic strategies enabling a natural defence against antibiotics and the induction of mechanisms in increasing resistance to the used antibacterial chemicals. The mechanisms presented in this review developed by the bacteria have a significant impact on reducing the ability to combat bacterial infections in humans and animals. Moreover, the high prevalence of multi-resistant strains in the environment and the ease of transmission of drug-resistance genes between the different bacterial species including commensal flora and pathogenic like foodborne pathogens (E. coli, Campylobacter spp., Enterococcus spp., Salmonella spp., Listeria spp., Staphylococcus spp.) favor the rapid spread of multi-resistance among bacteria in humans and animals. Given the global threat posed by the widespread phenomenon of multi-drug resistance among bacteria which are dangerous for humans and animals, the subject of this study is the presentation of the mechanisms of resistance in most frequent bacteria called as “foodborne pathoges” isolated from human and animals. In order to present the significance of the global problem related to multi-drug resistance among selected pathogens, especially those danger to humans, the publication also presents statistical data on the percentage range of occurrence of drug resistance among selected bacteria in various regions of the world. In addition to the phenotypic characteristics of pathogen resistance, this review also presents detailed information on the detection of drug resistance genes for specific groups of antibiotics. It should be emphasized that the manuscript also presents the results of own research i.e., Campylobacter spp., E. coli or Enetrococcus spp. This subject and the presentation of data on the risks of drug resistance among bacteria will contribute to initiating research in implementing the prevention of drug resistance and the development of alternatives for antimicrobials methods of controlling bacteria.

Bacteria that have become resistant to antibiotics, also known as superbugs,pose a huge threat to the human population. This is because these developed resistance to antibiotics. Antibiotics are a type of medicine that fights bacteria by either killing it or preventing it from growing. Although antibiotics make the once deadly now easily treatable, they can become ineffective as bacteria develop resistance to the antibiotic, causing diseases to become potentially fatal once more. Thus, scientists are rushing to find solutions in this arms race against evolving bacteria by either evolving current antibiotics or discovering new stands to fight evolving bacteria. In order to discover whether bacteria can develop resistance to household antibiotics, a controlled experiment was conducted. This was done by growing bacteria on agar plates with antibiotic ointments applied (in dilution series) to see if antibiotic resistance could build. Theorizing that by lowering the concentration of over the counter antibiotics, resistant bacteria would be selected and my bacterial population would evolve antibiotic resistance.In conclusion of the experiment antibiotic resistance did appear as a trait, but the level of it was inconsistent across the different bacteria populations.

In a clinical infection, multiplying and non-multiplying bacteria co-exist. Antibiotics kill multiplying bacteria, but they are very inefficient at killing non-multipliers which leads to slow or partial death of the total target population of microbes in an infected tissue. This prolongs the duration of therapy, increases the emergence of resistance and so contributes to the short life span of antibiotics after they reach the market. Targeting non-multiplying bacteria from the onset of an antibiotic development program is a new concept. This paper describes the proof of principle for this concept, which has resulted in the development of the first antibiotic using this approach. The antibiotic, called HT61, is a small quinolone-derived compound with a molecular mass of about 400 Daltons, and is active against non-multiplying bacteria, including methicillin sensitive and resistant, as well as Panton-Valentine leukocidin-carrying Staphylococcus aureus. It also kills mupirocin resistant MRSA. The mechanism of action of the drug is depolarisation of the cell membrane and destruction of the cell wall. The speed of kill is within two hours. In comparison to the conventional antibiotics, HT61 kills non-multiplying cells more effectively, 6 logs versus less than one log for major marketed antibiotics. HT61 kills methicillin sensitive and resistant S. aureus in the murine skin bacterial colonization and infection models. No resistant phenotype was produced during 50 serial cultures over a one year period. The antibiotic caused no adverse affects after application to the skin of minipigs. Targeting non-multiplying bacteria using this method should be able to yield many new classes of antibiotic. These antibiotics may be able to reduce the rate of emergence of resistance, shorten the duration of therapy, and reduce relapse rates

Horizontal gene transfer (HGT) and gene duplication are often considered as separate mechanisms driving the evolution of new functions. However, the mobile genetic elements (MGEs) implicated in HGT can copy themselves, so positive selection on MGEs could drive gene duplications. Here, we use a combination of modeling and experimental evolution to examine this hypothesis and use long-read genome sequences of tens of thousands of bacterial isolates to examine its generality in nature. Modeling and experiments show that antibiotic selection can drive the evolution of duplicated antibiotic resistance genes (ARGs) through MGE transposition. A key implication is that duplicated ARGs should be enriched in environments associated with antibiotic use. To test this, we examined the distribution of duplicated ARGs in 18,938 complete bacterial genomes with ecological metadata. Duplicated ARGs are highly enriched in bacteria isolated from humans and livestock. Duplicated ARGs are further enriched in an independent set of 321 antibiotic-resistant clinical isolates. Our findings indicate that duplicated genes often encode functions undergoing positive selection and horizontal gene transfer in microbial communities.

A yearlong study was performed to examine the effect of antibiotic administration on the bacterial gut flora. Gram-negative facultative anaerobic bacteria were recovered from the feces of healthy adult volunteers administered amoxicillin, minocycline or placebo, and changes determined in antimicrobial resistance (AMR) gene carriage. Seventy percent of the 1039 facultative anaerobic isolates recovered were identified by MALDI-TOF as Escherichia coli. A microarray used to determine virulence and resistance gene carriage demonstrated that AMR genes were widespread in all administration groups, with the most common resistance genes being bla TEM, dfr, strB, tet(A), and tet(B). Following amoxicillin administration, an increase in the proportion of amoxicillin resistant E. coli and a three-fold increase in the levels of bla TEM gene carriage was observed, an effect not observed in the other two treatment groups. Detection of virulence genes, including stx1A, indicated not all E. coli were innocuous commensals. Approximately 150 E. coli collected from 6 participants were selected for pulse field gel electrophoresis (PFGE), and a subset used for characterisation of plasmids and Phenotypic Microarrays (PM). PFGE indicated some E. coli clones had persisted in volunteers for up to 1 year, while others were transient. Although there were no unique characteristics associated with plasmids from persistent or transient isolates, PM assays showed transient isolates had greater adaptability to a range of antiseptic biocides and tetracycline; characteristics which were lost in some, but not all persistent isolates. This study indicates healthy individuals carry bacteria harboring resistance to a variety of antibiotics and biocides in their intestinal tract. Antibiotic administration can have a temporary effect of selecting bacteria, showing co-resistance to multiple antibiotics, some of which can persist within the gut for up to 1 year

The increasing resistance of harmful biological organisms (bacteria, parasites, and pests) to selection pressure from the widespread use of control agents such as antibiotics, antimalarials, and pesticides is a serious problem in both medicine and agriculture. Modeling resistance —or, conversely, the effectiveness of these control agents as a biological resource—yields insights into how these agents should be optimally managed to maximize their economic benefit to society. This paper uses a model of evolution of bacterial resistance to antibiotics—in which resistance places an evolutionary disadvantage on the resistant organism—to develop a simple sequential algorithm of optimal antibiotic use. Although the solution to this problem follows the well-recognized rule of using resources in the order of increasing marginal cost, the unique ways in which these economic costs arise from differing biological traits distinguishes this problem from others in the natural resources arena. This paper also examines the option of periodically rotating between two or more antibiotics and characterizes the economic and biological criteria under which a cycling strategy is superior to simultaneous use of two or more antibiotics.antibiotic resistance, natural resource, optimization.

Transposons are a group of mobile genetic elements that are defined as a DNA sequence. Transposons can jump into different places of the genome; for this reason, they are called jumping genes. However, some transposons are always kept at the insertion site in the genome. Most transposons are inactivated and as a result, cannot move. Transposons are divided into two main groups: retrotransposons (class І) and DNA transposons (class ІІ). Retrotransposons are often found in eukaryotes. DNA transposons can be found in both eukaryotes and prokaryotes. The bacterial transposons belong to the DNA transposons and the Tn family, which are usually the carrier of additional genes for antibiotic resistance. Transposons can transfer from a plasmid to other plasmids or from a DNA chromosome to plasmid and vice versa that cause the transmission of antibiotic resistance genes in bacteria. The treatment of bacterial infectious diseases is difficult because of existing antibiotic resistance that part of this antibiotic resistance is caused by transposons. Bacterial infectious diseases are responsible for the increasing rise in world mortality rate. In this review, transposons and their roles have been studied in bacterial antibiotic resistance, in detail.

The introduction of β-lactam antibiotics (penicillins and cephalosporins) in the 1940s and 1950s probably represents the most dramatic event in the battle against infection in human medicine. Even before widespread global use of penicillin, resistance was already recorded. E. coli producing a penicillinase was reported in Nature in 1940 (Abraham, 1940) and soon after a similar penicillinase was discovered in Staphylococcus aureus (Kirby, 1944). The appearance of these genes, so quickly after the discovery and before the widespread introduction of penicillin, clearly shows that the resistance genes pre-dated clinical use of the antibiotic itself

The emergence of antibiotic resistance mechanisms among bacterial pathogens increases the demand for novel treatment strategies. Lately, the contribution of non-coding RNAs to antibiotic resistance and their potential value as drug targets became evident. RNA attenuator elements in mRNA leader regions couple expression of resistance genes to the presence of the cognate antibiotic. Trans-encoded small RNAs (sRNAs) modulate antibiotic tolerance by base-pairing with mRNAs encoding functions important for resistance such as metabolic enzymes, drug efflux pumps, or transport proteins. Bacteria respond with extensive changes of their sRNA repertoire to antibiotics. Each antibiotic generates a unique sRNA profile possibly causing downstream effects that may help to overcome the antibiotic challenge. In consequence, regulatory RNAs including sRNAs and their protein interaction partners such as Hfq may prove useful as targets for antimicrobial chemotherapy. Indeed, several compounds have been developed that kill bacteria by mimicking ligands for riboswitches controlling essential genes, demonstrating that regulatory RNA elements are druggable targets. Drugs acting on sRNAs are considered for combined therapies to treat infections. In this review, we address how regulatory RNAs respond to and establish resistance to antibiotics in bacteria. Approaches to target RNAs involved in intrinsic antibiotic resistance or virulence for chemotherapy will be discussed.

The minimum antibiotic concentrations for selecting an R plasmid in vivo were determined in germfree rates colonized by two isogenic strains of Escherichia coli, one of which carried an R plasmid. Seventy groups of three gnotobiotic mice were given low doses of ampicillin, colistin, flumequin, gentamicin, tetracycline, or streptomycin via drinking water for 2 weeks. The equilibrium between susceptible and resistant populations of bacteria was monitored daily in feces and compared with that of control mice given pure water. This model yielded reproducible data, and dose and response were strongly correlated. The minimum selecting doses ranged from 0.9 te 12.8 µg/ml of water, depending on the antibiotic and the R plasmid. The use of mathematical models and complementary in vitro experiments accounted for the effect of the low antibiotic levels

Hospital wastewater tends to be a hotspot for the environmental spread of antibiotic resistance, as recent studies have shown that antibiotic residues, resistant bacteria, and resistant genes occur in aquatic environments. The present study reports antibiotic residues, bacteria that are resistant to antibiotics, and genes associated with antibiotic resistance in hospital wastewater in Sri Lanka. The highest concentration of AMX (0.001-0.024 µg/ml) and AMP (0.001-0.023 µg/ml) among the selected antibiotics were detected in hospital wastewater effluent. The antibiotic-resistant pathogenic bacteria, E. coli (31 %), Staphylococcus sp. (23%), Acinetobacter sp. (19%), Streptococcus sp. (10%), Pseudomonas aerugenosa (8%), Klebsiella pneumonia (6%), Moraxella sp. (3%), Aeromonas hydrophila (1%) and Streptomyces sp. (1%) were found as indigenous bacteria which indicate increase the risk of ARGs which directly effect on public health. The study's findings made apparent the significance of developing a specific treatment plant at the site to remove antibiotics before discharging hospital wastewater to the natural environment. Therefore, it is necessary to develop and apply innovative treatment technologies as a national policy to protect people from silent killers who will no longer be susceptible to antibiotics in the future, which has been identified as a challenge in the health sector.

The 4th ASM Conference on Antimicrobial Resistance in Zoonotic Bacteria and Foodborne Pathogens will continue and expand the excellent existing scientific agenda to include emphases on novel approaches to molecular typing, whole genome sequencing and its role in understanding the evolution and dissemination of AMR bacteria, host adaptation and specificity, metagenome-based studies of resistance, isolate-based versus sample-based inference, risk assessment, and computational biology and mathematical modeling

The production and use of antibiotics are becoming increasingly common worldwide, and the problem of antibiotic resistance is increasing alarmingly. Drug‐resistant infections threaten human life and health and impose a heavy burden on the global economy. The origin and molecular basis of bacterial resistance is the presence of antibiotic resistance genes (ARGs). Investigations on ARGs mostly focus on the environments in which antibiotics are frequently used, such as hospitals and farms. This literature review summarizes the current knowledge of the occurrence of antibiotic‐resistant bacteria in nonclinical environments, such as air, aircraft wastewater, migratory bird feces, and sea areas in‐depth, which have rarely been involved in previous studies. Furthermore, the mechanism of action of plasmid and phage during horizontal gene transfer was analyzed, and the transmission mechanism of ARGs was summarized. This review highlights the new mechanisms that enhance antibiotic resistance and the evolutionary background of multidrug resistance; in addition, some promising points for controlling or reducing the occurrence and spread of antimicrobial resistance are also proposed.

Chemotherapeutic agents have been developed for treating bacterial infections and have been widely used for cultured fish for the last 30 years in Japan. The extensive use of chemotherapeutants has resulted in an increase in the occurrence of drug resistance in fish-pathogenic bacteria and also in the bacterial flora of the intestinal tract of cultured fish. The kinds of chemotherapeutants used are correlated with the occurrence of the corresponding drug-resistant genes in fish-pathogenic bacteria. Almost all multiple-drug resistant strains are carried on the transferable R plasmid, although resistance in fish pathogens to nitrofuran derivatives and pyridonecarboxylic acids is associated with a chromosomal gene. The DNA sequences of R plasmids generally differ depending on the species of fish pathogen. Exceptions are the R plasmids of Aeromonas hydrophila and A. salmonicida, which have the same resistance markers as chloramphenicol, streptomycin, and sulfonamides (SA); and the R plasmids of A. hydrophila and Edwardsiella tarda, which have the same resistance markers as SA and tetracycline. The fish pathogens A. hydrophila, A. salmonicida, E. tarda, Enterococcus seriolicida, Pasteurella piscicida, and Vibrio anguillarum are all widely distributed in fish farms in various areas, and within each species the R plasmid has an identical DNA sequence. The chloramphenicol resistance (cat) gene of the R plasmid from Gram-negative bacteria was classified into CAT I, II, III, and IV according to the DNA sequence. The cat gene of P. piscicida was classified as CAT I, those of A. salmonicida and E. tarda were classified as CAT II, and that of V. anguillarum was classified as CAT II or IV, depending on the time the strains were isolated. The tetracycline-resistance determinants (Tet), which occur in six classes (Tet A through Tet G), were class D in the R plasmids obtained from strains of V. anguillarum that were isolated from 1989 to 1991. The Tet for strains of V. anguillarum isolated from 1973 to 1977 was classified as Tet B, while for strains isolated from 1980 to 1983 it was classified as Tet G

Plant growth-promoting bacteria (PGPB) are endowed with several attributes that can be beneficial for host plants. They opened myriad doors toward green technology approach to reduce the use of chemical inputs, improve soil fertility, and promote plants’ health. However, many of these PGPB harbor antibiotic resistance genes (ARGs). Less attention has been given to multi-resistant bacterial bioinoculants which may transfer their ARGs to native soil microbial communities and other environmental reservoirs including animals, waters, and humans. Therefore, large-scale inoculation of crops by ARGs-harboring bacteria could worsen the evolution and dissemination of antibiotic resistance and aggravate the negative impacts on such ecosystem and ultimately public health. Their introduction into the soil could serve as ARGs invasion which may inter into the food chain. In this review, we underscore the antibiotic resistance of plant-associated bacteria, criticize the lack of consideration for this phenomenon in the screening and application processes, and provide some recommendations as well as a regulation framework relating to the development of bacteria-based biofertilizers to aid maximizing their value and applications in crop improvement while reducing the risks of ARGs invasion.

The discovery and use of antibiotics in the chemotherapy of bacterial infections has revolutionised medicine as it is today. Unfortunately, the progressive use of antibiotics has promoted the evolution of bacterial defences against these mediators and thus the emergence of antibiotic resistance. Multidrug resistance (MDR) in bacterial pathogens has grown with such rapid progression that it now threatens to compromise the effective chemotherapy of a plethora of diseases. This thesis aspires to elucidate the molecular resistance mechanisms adopted by these bacteria, in order to expand our knowledge and to assist in the development of new therapeutic approaches to circumvent these mechanisms. On this basis, this thesis presents insights into a novel Vibrio cholerae antibiotic resistance, var, operon that encodes a metallo- β -lactamase (Mßl), VarG, and a tripartite ATP-binding cassette-type (ABC-type) transport system, VarACDEF that has substrate specificities for antimicrobial peptides and macrolide antibiotics. Mßls are fast emerging as a primary resistance mechanism, possibly as a consequence of the introduction of newer ß-lactam antibiotics such as the carbapenems in response to increasing Gram-negative bacterial resistance. Fascinatingly, the ABC transporter, through secondary structure predictions, has been envisaged to adopt a tripartite structure similar to the MDR transporter, AcrAB-TolC, from the resistance nodulation and cell division (RND) family. The structural characterisation of this system would be the first such tripartite system to be elucidated and may bring new insights into how Gram-negative bacteria may have evolved to tackle the issue that threatens its existence. The resistance mechanisms in the var Operon are believed to be under the control of a LysR-type transcriptional regulatory protein (LTTR), VarR. LTTR proteins form one of the largest transcriptional regulatory families with extremely diverse functions ranging from amino acid biosynthesis to CO(_2) fixation. VarR binds to three distinct promoter regions, varRG, varGA and varBC located upstream and adjacent to VarG, VarA an AcrA-like membrane fusion protein and VarC a TolC-like outer membrane protein, respectively. VarR has also been shown to act as a repressor at the varRG promoter region in the absence of its substrate. Interestingly, the mechanism of regulation by VarR is strikingly similar to the well documented LTTR, AmpR and serine ß-lactamase AmpC system that are found in many pathogenic bacteria. It could be that V. cholerae has evolved from this regular system and developed a ß-lactamase that would prove more beneficial in light of current selective pressures. Contrary to LTTRs being notoriously recalcitrant to purification due to their low solubility, this thesis reports the successful purification and crystallisation of full-length VarR in the presence and absence of its cognate promoter DNA. Elucidating the structural characteristics of VarR would be the first such regulator associated with MDR in the LTTR family. This would advance the knowledge on the only currently existing full-length crystal structure of a LTTR, CbnR, and will provide further insights into how structural conformations may lead to dissociation from the promoter and induction of gene expression. Understanding the mechanism by which VarR induces expression of these resistance mechanisms is paramount for future strategies to prevent the emergence of MDR microorganisms. Although these mechanisms of MDR maybe elucidated in V. cholerae, the evolutionary relatedness and conservation of structure and function in all families will enable this information to be related to similar systems in alternative bacterial species