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PubMed1998

In vivo characterization of the drug resistance profile of the major ABC transporters and other components of the yeast pleiotropic drug resistance network.

Multidrug resistance (MDR) mediated by broad specificity transporters is one of the most important strategies used by pathogens, including cancer cells, to evade chemotherapy. In the yeast Saccharomyces cerevisiae, a complex pleiotropic drug resistance (PDR) network of genes involved in MDR is composed of the transcriptional regulators Pdr1p and Pdr3p, which activate expression of the ATP-binding cassette (ABC) MDR transporters-encoding genes PDR5, SNQ2, and YOR1 as well as other not yet identified genes. We have screened 349 toxic compounds in isogenic S. cerevisiae strains deleted of PDRS, SNQ2, or YOR1 in different combinations as well as both PDR1 and PDR3. The screen revealed extremely promiscuous, yet limited, and to a large extent overlapping but distinct drug resistance profiles of Pdr5p, Snq2p, and Yor1p. These ABC-MDR transporters mediated resistance to most currently available classes of clinically and agriculturally important fungicides and also to many antibiotics, herbicides, and others. Several classes of compounds were identified for the first time in the drug resistance spectrum of MDR transporters. These are fungicides, such as anilinopyrimidines, benzimidazoles, benzenedicarbonitriles, dithiocarbamates, guanidines, imidothiazoles, polyenes, pyrimidynyl carbinols, and strobilurine analogues; the urea derivative and anilide herbicides; flavonoids, several membrane lipids resembling detergents; and newly synthesized lysosomotropic aminoesters; as well as many others. Identification of compounds showing Pdr1p, Pdr3p-dependent, but Pdr5p-, Snq2p-, and Yor1p-independent toxicity, reflected in the case of rhodamine 6G, by efflux alterations, suggests the involvement of new drug resistance genes and is a first step toward their identification. The highly increased toxicity of bile acids toward the PDR1, PDR3 double disruptant together with the decreased level of BAT1 promoter dependent beta-galactosidase activity suggest that the Bat1p ABC transporter is a new member of the PDR network. Our results may contribute to a better understanding of the mechanism of MDR, in particular in the pathogenic yeast Candida albicans. They also provide and indication of the physiological function of MDR transporters and suggest new approaches for the cloning of the mammalian bile acid transporters.

ATP-Binding Cassette Transporters↗

PubMed2003

Alkylaminoquinolines inhibit the bacterial antibiotic efflux pump in multidrug-resistant clinical isolates.

Over the last decade, MDR (multidrug resistance) has increased worldwide in microbial pathogens by efflux mechanisms, leading to treatment failures in human infections. Several Gram-negative bacteria efflux pumps have been described. These proteinaceous channels are capable of expelling structurally different drugs across the envelope and conferring antibiotic resistance in various bacterial pathogens. Combating antibiotic resistance is an urgency and the blocking of efflux pumps is an attractive response to the emergence of MDR phenotypes in infectious bacteria. In the present study, various alkylaminoquinolines were tested as potential inhibitors of drug transporters. We showed that alkylaminoquinolines are capable of restoring susceptibilities to structurally unrelated antibiotics in clinical isolates of MDR Gram-negative bacteria. Antibiotic efflux studies indicated that 7-nitro-8-methyl-4-[2'-(piperidino)ethyl]aminoquinoline acts as an inhibitor of the AcrAB-TolC efflux pump and restores a high level of intracellular drug concentration. Inhibitory activity of this alkylaminoquinoline is observed on clinical isolates showing different resistance phenotypes.

Aminoquinolines↗

PubMed2003

ABC transporters of the wheat pathogen Mycosphaerella graminicola function as protectants against biotic and xenobiotic toxic compounds.

We have studied the role of five ABC transporter genes (MgAtr to MgAtr5) from the wheat pathogen Mycosphaerella graminicola in multidrug resistance (MDR). Complementation of Saccharomyces cerevisiae mutants with the ABC transporter genes from M. graminicola showed that all the genes tested encode proteins that provide protection against chemically unrelated compounds, indicating that their products function as multidrug transporters with distinct but overlapping substrate specificities. Their substrate range in yeast includes fungicides, plant metabolites, antibiotics, and a mycotoxin derived from Fusarium graminearum (diacetoxyscirpenol). Transformants of M. graminicola in which individual ABC transporter genes were deleted or disrupted did not exhibit clear-cut phenotypes, probably due to the functional redundancy of transporters with overlapping substrate specificity. Independently generated MgAtr5 deletion mutants of M. graminicola showed an increase in sensitivity to the putative wheat defence compound resorcinol and to the grape phytoalexin resveratrol, suggesting a role for this transporter in protecting the fungus against plant defence compounds. Bioassays with antagonistic bacteria indicated that MgAtr2 provides protection against metabolites produced by Pseudomonas fluorescens and Burkholderia cepacia. In summary, our results show that ABC transporters from M. graminicola play a role in protection against toxic compounds of natural and artificial origin.

ATP-Binding Cassette Transporters↗

PubMed2006

Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center.

Military medical facilities treating patients injured in Iraq and Afghanistan have identified a large number of multidrug-resistant (MDR) Acinetobacter baumannii isolates. In order to anticipate the impact of these pathogens on patient care, we analyzed the antibiotic resistance genes responsible for the MDR phenotype in Acinetobacter sp. isolates collected from patients at the Walter Reed Army Medical Center (WRAMC). Susceptibility testing, PCR amplification of the genetic determinants of resistance, and clonality were determined. Seventy-five unique patient isolates were included in this study: 53% were from bloodstream infections, 89% were resistant to at least three classes of antibiotics, and 15% were resistant to all nine antibiotics tested. Thirty-seven percent of the isolates were recovered from patients nosocomially infected or colonized at the WRAMC. Sixteen unique resistance genes or gene families and four mobile genetic elements were detected. In addition, this is the first report of bla(OXA-58)-like and bla(PER)-like genes in the U.S. MDR A. baumannii isolates with at least eight identified resistance determinants were recovered from 49 of the 75 patients. Molecular typing revealed multiple clones, with eight major clonal types being nosocomially acquired and with more than 60% of the isolates being related to three pan-European types. This report gives a "snapshot" of the complex genetic background responsible for antimicrobial resistance in Acinetobacter spp. from the WRAMC. Identifying genes associated with the MDR phenotype and defining patterns of transmission serve as a starting point for devising strategies to limit the clinical impact of these serious infections.

Acinetobacter↗

PubMed2004

Bacterial population changes in hospital effluent treatment plant in central India.

Hospital effluent with its high content of multidrug resistant (MDR) enterobacteria and the presence of enteric pathogens could pose a grave problem for the community. It was planned at our tertiary care hospital in central India to study the population changes at various steps of effluent treatment plant (ETP) like collection, aeration, clarification, liquid sludge, dried sludge, high-pressure filter and treated wastewater. The study included viable bacterial counts, coliform counts, staphylococcal, enterococcal, Pseudomonas and multiple drug resistant (MDR) gram negative bacterial counts in the different stages of ETP. In order to study the distribution of bacteria as free floating in liquid and adherent to suspended particles, enumeration of the bacteria in the filterate and the sediment was also carried out. The effluent input showed 55% of the 8.6 x 10(6)/ml bacteria as coliforms and E. coli which was a typical of fecal flora. The prevalence of MDR coliforms was 0.26%. The substantial reduction (> 3log) was seen for the effluent coming from the clarifier. The bulk of the bacteria in the hospital effluent remains firmly adhered to solid particles; aeration and clarification removes bulk of the bacteria by physical processes like flocculation. The treated liquid effluent still contains sizeable loads of MDR bacteria and inactivation by procedure such as chlorination is required. The bacteria get concentrated in sludge and a greater concentration of chlorine is required for decontamination.

Bacteria↗

PubMed2005

[Drug resistance of Mycobacteria tuberculosis in patients with new-onset pulmonary tuberculosis].

Statistics for the last 6 years show a trend to growing number of new cases with tuberculosis of the lungs with drug-resistant pathogen. In recurrent tuberculosis multiple drug resistance (MDR) was three times higher than in new cases. Treatment efficacy depended on MDR and patients' compliance. The results of the basic treatment course were unstable: many patients had exacerbation within 3-4 years after therapy, many patients died, especially those with M. tuberculosis resistant to many drugs.

Antibiotics, Antitubercular↗

PubMed2003

Characterization of Salmonella enterica serotype newport isolated from humans and food animals.

Salmonella enterica serotype Newport isolates resistant to at least nine antimicrobials (including extended-spectrum cephalosporins), known as serotype Newport MDR-AmpC isolates, have been rapidly emerging as pathogens in both animals and humans throughout the United States. Resistance to extended-spectrum cephalosporins is associated with clinical failures, including death, in patients with systemic infections. In this study, 87 Salmonella serotype Newport strains were characterized by pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility testing and examined for the presence of class 1 integrons and bla(CMY) genes. Thirty-five PFGE patterns were observed with XbaI, and three of these patterns were indistinguishable among isolates from humans and animals. Fifty-three (60%) Salmonella serotype Newport isolates were identified as serotype Newport MDR-AmpC, including 16 (53%) of 30 human isolates, 27 (93%) of 29 cattle isolates, 7 (70%) of 10 swine isolates, and 3 (30%) of 10 chicken isolates. However, 28 (32%) Salmonella serotype Newport isolates were susceptible to all 16 antimicrobials tested. The bla(CMY) gene was present in all serotype Newport MDR-AmpC isolates. Furthermore, the plasmid-mediated bla(CMY) gene was transferable via conjugation to an Escherichia coli strain. The transconjugant showed the MDR-AmpC resistance profile. Thirty-five (40%) of the isolates possessed class 1 integrons. Sequence analyses of the integrons showed that they contained aadA, which confers resistance to streptomycin, or aadA and dhfr, which confer resistance to trimethoprim-sulfamethoxazole. One integron from a swine isolate contained the sat-1 gene, which encodes resistance to streptothricin, an antimicrobial agent that has never been approved for use in the United States. In conclusion, Salmonella serotype Newport MDR-AmpC was commonly identified among Salmonella serotype Newport isolates recovered from humans and food animals. These findings support the possibility of transmission of this organism to humans through the food chain.

Animals↗

PubMed1993

Drug resistance and the P-glycoprotein homologues of Plasmodium falciparum.

The chloroquine resistance phenotype of Plasmodium falciparum shares many similarities to multi-drug resistance in tumour cells and this has led to the identification of two mdr-like genes (pfmdr1, pfmdr2) from this human pathogen. The pfmdr1 gene has been linked to the chloroquine resistance phenotype, although a genetic cross appears to contradict these results. Analysis of drug resistant mutants selected in vitro has shown that the level of expression of the pfmdr1 gene can affect resistance to chloroquine, mefloquine, halofantrine and quinine. Mefloquine isolates from the field appear to always contain amplified levels of the pfmdr1 gene and also overexpress the transcript. They are also resistant to halofantrine suggesting a true multi-drug resistant phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Survival of Salmonella enterica serovar Newport in manure and manure-amended soils.

Salmonella enterica serovar Newport has undergone a rapid epidemic spread in dairy cattle. This provides an efficient mechanism for pathogen amplification and dissemination into the environment through manure spreading on agricultural land. The objective of this study was to determine the survival characteristics of Salmonella serovar Newport in manure and manure-amended soils where the pathogen may be amplified. A multidrug-resistant (MDR) Salmonella serovar Newport strain and a drug-susceptible (DS) strain, both bovine isolates, were inoculated into dairy manure that was incubated under constant temperature and moisture conditions alone or after being mixed with sterilized or nonsterilized soil. Salmonella serovar Newport concentrations increased by up to 400% in the first 1 to 3 days following inoculation, and a trend of steady decline followed. With manure treatment, a sharp decline in cell concentration occurred after day 35, possibly due to microbial antagonism. For all treatments, decreases in Salmonella serovar Newport concentrations over time fit a first-order kinetic model. Log reduction time was 14 to 32 days for 1 log(10), 28 to 64 days for 2 log(10), and 42 to 96 days for 3 log(10) declines in the organisms' populations from initially inoculated concentrations. Most-probable-number monitoring data indicated that the organisms persisted for 184, 332, and 405 days in manure, manure-amended nonsterilized soil, and manure-amended sterilized soil, respectively. The MDR strain and the DS strain had similar survival patterns.

Animals↗

PubMed2002

The multidrug resistance transporters of the major facilitator superfamily, 6 years after disclosure of Saccharomyces cerevisiae genome sequence.

The emergence of multidrug resistance (MDR) plays a crucial role in the failure of treatments of tumors and infectious diseases and in the control of plant pathogens, weeds and food-poisoning and food-spoilage microorganisms. Among the mechanisms underlying the MDR phenomenon in various organisms is the action of transmembrane transport proteins that presumably catalyse the active expulsion of structurally and functionally unrelated cytotoxic compounds out of the cell or their intracellular partitioning. On the basis of the complete genome sequence of Saccharomyces cerevisiae, numerous established and putative multidrug transporters were identified in this non-pathogenic, easy to manipulate eukaryotic model system. In yeast, the putative drug:H(+)-antiporters belong to the major facilitator superfamily; they comprise at least 23 proteins that have largely escaped characterisation by classical approaches. Other MDR determinants are membrane transporters belonging to the ATP binding cassette (ABC) superfamily, that utilize the energy of ATP hydrolysis for activity, and factors for transcriptional regulation of all the MDR transporters. This work reviews the current status of knowledge on the poorly characterized H(+)-antiporters, with 12 and 14 predicted spans, DHA12 and DHA14, drug efflux families. Consideration is given to the inventory and phylogenetic characterization, role as MDR determinants, regulation of gene expression, subcellular localisation and activity as solute transporters. Most of the present knowledge on these putative drug:H(+)-antiporters was driven by disclosure of S. cerevisiae genome sequence, in April 1996, being a paradigm of post-genomic research.

Drug Resistance, Multiple, Fungal↗

PubMed2002

Drug resistance in yeasts--an emerging scenario.

In view of the increasing threat posed by fungal infections in immunocompromised patients and due to the non-availability of effective treatments, it has become imperative to find novel antifungals and vigorously search for new drug targets. Fungal pathogens acquire resistance to drugs (antifungals), a well-established phenomenon termed multidrug resistance (MDR), which hampers effective treatment strategies. The MDR phenomenon is spread throughout the evolutionary scale. Accordingly, a host of responsible genes have been identified in the genetically tractable budding yeast Saccharomyces cerevisiae, as well as in a pathogenic yeast Candida albicans. Studies so far suggest that, while antifungal resistance is the culmination of multiple factors, there may be a unifying mechanism of drug resistance in these pathogens. ABC (ATP binding cassette) and MFS (major facilitator superfamily) drug transporters belonging to two different superfamilies, are the most prominent contributors to MDR in yeasts. Considering the abundance of the drug transporters and their wider specificity, it is believed that these drug transporters may not exclusively export drugs in fungi. It has become apparent that the drug transporters of the ABC superfamily of S. cerevisiae and C. albicans are multifunctional proteins, which mediate important physiological functions. This review summarizes current research on the molecular mechanisms underlying drug resistance, the emerging regulatory circuits of MDR genes, and the physiological relevance of drug transporters.

ATP-Binding Cassette Transporters↗

PubMed2003

Role of mechanical ventilation & development of multidrug resistant organisms in hospital acquired pneumonia.

BACKGROUND & OBJECTIVES: Among hospital-acquired infections, pneumonia is considered to be the leading cause of death mainly in patients with mechanical ventilation in intensive care units (ICUs). The present study was undertaken to estimate the occurrence of hospital-acquired pneumonia (HAP) as well as ventilator-associated pneumonia (VAP) along with the effect of different variables and to detect the presence of multi drug resistant (MDR) organisms in the intensive care unit (ICU). METHODS: Of the 328 patients admitted in the ICU during 2001, 241 stayed for > 72 h and 148 were ventilated. The respiratory specimens collected from the cases and controls were sent for cytology, bacterial culture and antimicrobial sensitivity. RESULTS: The overall rate of HAP was 53.9 per cent, mortality rate was 47.3 per cent and attributable risk of mortality with ventilator was 72.3 per cent. Occurrence of VAP was 81.7 per cent. The rate of acquisition of HAP increased along with the duration of stay in the ICU. Of the total bacterial isolates, 96.2 per cent were obtained from patients on ventilator, an overall preponderance of Gram-negative bacteria, commonest being Pseudomonas spp along with 16.3 per cent polymicrobial infection was found in ICU. A significant number of ICU isolates were MDR in comparison to those from the non-ICU settings. INTERPRETATION & CONCLUSION: Mechanical ventilation and duration of ICU stay emerged as important risk factors for the development of HAP and VAP. MDR Gram-negative bacilli were the commonest respiratory pathogens responsible for increased mortality in patients with VAP.

Case-Control Studies↗

PubMed2004

Virulence characteristics and phylogenetic background of multidrug-resistant and antimicrobial-susceptible clinical isolates of Escherichia coli from across the United States, 2000-2001.

BACKGROUND: Increases in antimicrobial resistance in Escherichia coli have been paralleled by an increasing incidence of E. coli sepsis, suggesting a possible link between resistance and virulence. METHODS: All 76 multidrug-resistant (MDR) E. coli isolates (i.e., those resistant to > or =3 antimicrobial agents, including ampicillin, ceftazidime, trimethoprim-sulfamethoxazole, gentamicin, and ciprofloxacin) reported to the Tracking Resistance in the United States Today studies during 2000-2001 and 76 closely matched pansusceptible control isolates were studied. Extended virulence profiles and E. coli phylogenetic group (A, B1, B2, or D) were compared between groups. RESULTS: The MDR isolates, which represented predominantly non-B2 phylogenetic groups (91%), exhibited significantly reduced molecular virulence, compared with the predominantly group B2-derived control isolates (58%). Only 30% of MDR isolates, compared with 61% of control isolates (P<.001), qualified as extraintestinal pathogenic E. coli (ExPEC), and even these isolates exhibited significantly lower virulence scores than did susceptible ExPEC (7.25 vs. 9.0; P=.001). Phylogenetic differences accounted for the apparent virulence differences between MDR and control isolates. CONCLUSIONS: These findings argue against a direct link between virulence traits and antimicrobial resistance in E. coli. Instead, they call into question why non-B2 strains are more commonly MDR, with differential exposure to selection pressure (including in agriculture) as one possible explanation.

Adhesins, Escherichia coli↗

PubMed2026

Multidrug resistance and genomic characteristics of nontypeable Haemophilus influenzae isolates from the respiratory tract of pediatric patients.

UNLABELLED: Nontypeable Haemophilus influenzae (NTHi) is a common colonizer of the human upper respiratory tract and one of the major pathogens responsible for pediatric respiratory tract infections. Given the increasing severity of its multidrug resistance (MDR), this study comprehensively investigated the genomic characteristics of circulating NTHi isolated from sputum and bronchoalveolar lavage fluid (BALF). A total of 104 H. influenzae isolates (69 from sputum; 35 from BALF) were collected from pediatric patients between January 2024 and January 2025. All isolates underwent whole-genome sequencing and antimicrobial susceptibility testing, followed by core/pan-genome phylogenetic analysis, multilocus sequence typing (MLST), and resistome profiling. Among them, 103 were identified as NTHi. We identified 29 known sequence types (STs) and 10 novel STs, with ST-107 (14.4%), ST-57 (10.6%), and ST-11 (8.7%) being the major circulating lineages. However, core-genome phylogenetic analysis provided a more granular view of the genetic variation within these identical STs. All the isolates showed high resistance to ampicillin (98.1%) and cefuroxime (84.6%). Genomically, the multidrug efflux pump gene hmrM was ubiquitous (100%). Ampicillin resistance was predominantly driven by blaTEM-1 carriage (77.9%), with minor contributions from chromosomal ftsI mutations. Fifteen plasmid replicons were predicted from 25 isolates, which highly coincided with the carriage of blaTEM-1 and other acquired resistance genes. This study demonstrates that MDR in pediatric NTHi is primarily driven by acquired resistance genes and chromosomal mutations, with specific resistant clones persisting and enriching under clinical antibiotic pressures. These findings underscore the importance of continuous high-resolution genomic surveillance in guiding rational antibiotic stewardship. IMPORTANCE: This study highlights the critical importance of high-resolution genomic surveillance in managing pediatric nontypeable Haemophilus influenzae (NTHi) infections. By utilizing whole-genome sequencing, we uncovered the pathogen's highly dynamic population structure and complex multidrug resistance (MDR) mechanisms. Crucially, our findings reveal a strong, non-random coupling between core genomic architectures, virulence factors, and MDR elements, driven by dual environmental and pharmacological pressures. This "virulence-MDR" co-evolutionary trend underscores the persistent clinical threat of locally adapted high-risk clones. These findings provide important insights for guiding rational clinical antibiotic stewardship, optimizing treatment strategies, and improving regional infection control.

Humans↗

PubMed2005

Multidrug resistance in yeast Candida.

The opportunistic human pathogens Candida albicans and other non-albicans species have acquired considerable significance in the recent past due to the enhanced susceptibility of immunocompromised patients. These pathogenic species of Candida derive their importance not only from the severity of their infections but also from their ability to develop resistance against antifungals. Widespread and prolonged use of azoles has led to the rapid development of the phenomenon of multidrug resistance (MDR), which poses a major hurdle in antifungal therapy. Various mechanisms that contribute to the development of MDR have been implicated in Candida as well as in other human fungal pathogens, and some of these include overexpression of or mutations in the target enzyme of azoles, lanosterol 14 alpha-demethylase, and transcriptional activation of genes encoding drug efflux pump proteins belonging to ATP-binding cassette (ABC) as well as to major facilitator superfamilies (MFS) of transporters. The ABC transporters, CDR1, CDR2, and an MFS pump CaMDR1, play a key role in azole resistance as deduced from their high level of expression found in several azole-resistant clinical isolates.

Antifungal Agents↗

PubMed2005

Chemosensitizers in drug transport mechanisms involved in protozoan resistance.

The emergence and spread of antiparasitic drug resistance pose a severe and increasing public health threat. Failures in prophylaxis or those in treatment with quinolines, hydroxynaphtoquinones, sesquiterpenic lactones, antifolate drugs, arsenic and antimony containing drugs sulfamides induce reemergence of parasitic-related morbidity and mortality. Resistance is often associated with alteration of drug accumulation into parasites, which results from a reduced uptake of the drug, an increased efflux or, a combination of the two processes. Resistance to quinolines, artemisinin derivatives and arsenicals and expression of an active efflux mechanism are more or less correlated in protozoa like Plasmodium spp., Leishmania spp., and Trypanosoma spp. Various parasite candidate genes have been proposed to be involved in drug resistance, each concerned in membrane transport. Genes encoding membrane glycoproteins, orthologue to the P-glycoproteins identified in MDR human cancer cells, have been described in these resistant pathogens in addition to various membrane proteins involved in drug transport. Several compounds have demonstrated, in the past decade, promising capability to reverse the drug resistance in parasite isolates in vitro, in animal models and for human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and derivatives, and anthracene derivatives. Here, are summarized the molecular bases of antiparasitic resistance emphasizing recent developments with compounds acting on trans-membrane proteins involved in drug efflux or uptake.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2026

A posttranslational modification of fimbriae drives pathogenicity in Klebsiella pneumoniae.

Antimicrobial resistance is a severe public health burden. Especially concerning are multidrug resistant (MDR) infections, which restrict treatment options and significantly increase mortality risk. A major cause of MDR infections worldwide is carbapenem-resistant Klebsiella pneumoniae (CRKp). The predominant CRKp sequence type worldwide is ST258. However, the factors underlying ST258's epidemic success are not well defined. Genomic analyses of clinical isolates of CRKp have found that the two-component regulatory system CrrAB is a genomic feature of ST258, suggesting that it may contribute to its global dominance. Despite this, the molecular details underpinning CrrAB's contribution to ST258 Kp biology and pathogenicity are poorly understood. We used RNA-sequencing to identify the regulon of CrrA and found that CrrAB induces the expression of a gene, encoding Crr-regulated fimbriae modifying protein (CfmP), that is essential for pathogenesis driven by this two-component system. We performed mass spectrometry analyses of fimbriae purified from Kp expressing or lacking cfmP and found that CfmP induces a novel oxidation to a histidine residue in the major pilin subunit of fimbriae, FimA. We demonstrate that this oxidation significantly increases host cell adhesion and high bacterial loads within the host. CrrAB also drives high antibiotic resistance in CRKp. Thus, our results place CrrAB at the intersection of pathogenicity and antibiotic resistance supporting its function as an important regulatory system driving the global dominance of ST258.

Klebsiella pneumoniae↗

PubMed2024

Tomato bacterial wilt disease outbreaks are accompanied by an increase in soil antibiotic resistance.

The presence of soil-borne disease obstacles and antibiotic resistance genes (ARGs) in soil leads to serious economic losses and health risks to humans. One area in need of attention is the evolution of ARGs as pathogenic soil gradually develops, which introduces uncertainty to the dynamic ability of conventional farming models to predict ARGs. Here, we investigated variations in tomato bacterial wilt disease accompanied by the resistome by metagenomic analysis in soils over 13 seasons of monoculture. The results showed that the abundance and diversity of ARGs and mobile genetic elements (MGEs) exhibited a significant and positive correlation with R. solanacearum. Furthermore, the binning approach indicated that fluoroquinolone (qepA), tetracycline (tetA), multidrug resistance genes (MDR, mdtA, acrB, mexB, mexE), and β-lactamases (ampC, blaGOB) carried by the pathogen itself were responsible for the increase in overall soil ARGs. The relationships between pathogens and related ARGs that might underlie the breakdown of soil ARGs were further studied in R. solanacearum invasion pot experiments. This study revealed the dynamics of soil ARGs as soil-borne diseases develop, indicating that these ecological trends can be anticipated. Overall, this study enhances our understanding of the factors driving ARGs in disease-causing soils.

Soil Microbiology↗