scholarly journals Global dissemination of tet(X3) and tet(X6) among livestock-associated Acinetobacter is sporadically mediated by highly diverse plasmidomes

2021 ◽  
Author(s):  
Kai Zhou ◽  
Yingying Cheng ◽  
Yang Liu ◽  
Yong Chen ◽  
Fuman Huang ◽  
...  
Keyword(s):  
Growth Rate ◽  
Phylogenetic Analysis ◽  
Environmental Samples ◽  
One Health ◽  
Clinical Effectiveness ◽  
Fold Increase ◽  
The Other ◽  
Swine Farm ◽  
High Level ◽  
Level Resistance

The emergence of plasmid-borne tet(X) genes mediates high-level resistance of tigecycline largely threatening its clinical effectiveness. Currently, the dissemination pattern of plasmid-borne tet(X) genes remains unclear. In this study, 684 fecal and environmental samples were collected at six livestock farms, and 15 tet(X)-positive Acinetobacter isolates were recovered, mainly including 9 tet(X3)- and 5 tet(X6)-positive A. towneri strains. A clonal dissemination of tet(X3)-positive A. towneri was detected in a swine farm, while the tet(X6)-positive A. towneri strains mainly sporadically disseminated in the same farm. A tet(X3)-carrying plasmid (pAT181) was self-transmissible from a tigecycline-susceptible A. towneri strain to A. baumannii ATCC17978, causing a 128-fold and 64-512-fold increase in the MIC values of tigecycline and the other tetracyclines, respectively. Worrisomely, pAT181 was stably maintained and increased the growth rate of ATCC17978. Further identification of tet(X)s in 10,680 Acinetobacter genomes retrieved from GenBank revealed that, tet(X3) (n=249) followed by tet(X5)-like (n=61) and tet(X6) (n=53) are the prevalent alleles mainly carried by four species, and most of them are livestock associated. Phylogenetic analysis showed that most of tet(X3) and tet(X6)-positive isolates disseminate sporadically. The structures of tet(X3) and tet(X6) plasmidomes are highly diverse and no epidemic plasmids have emerged yet. However, cross-species and cross-region transmissions of tet(X3) might have been mediated by several plasmids in a small proportion of strains. Our study evidence that tet(X3) and tet(X6) currently disseminate sporadically in Acinetobacter. Continuous surveillance for tet(X)s in the context of One Health is necessary to prevent them from transmitting to humans.

scholarly journals Phenotypic Characterization of Two Ancylostoma caninum Isolates with Different Susceptibilities to the Anthelmintic Pyrantel

2008 ◽  
Vol 52 (11) ◽  
pp. 3980-3986 ◽  
Author(s):  
Steven R. Kopp ◽  
Glen T. Coleman ◽  
James S. McCarthy ◽  
Andrew C. Kotze
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Resistance Mechanism ◽  
Fold Increase ◽  
Phenotypic Characterization ◽  
Gastrointestinal Helminths ◽  
Ancylostoma Caninum ◽  
High Level ◽  
Level Resistance

ABSTRACT The anthelmintic pyrantel plays an important role in the control of gastrointestinal helminths of humans and domestic animals. Despite the demonstration of pyrantel resistance in several helminth species over the last 20 years, the resistance mechanism remains unclear. It has been hypothesized that resistance may arise as a consequence of changes to the relative proportions of subpopulations of nicotinic acetylcholine receptors (nAchRs). To test this hypothesis, we examined the responses of two isolates of the canine hookworm Ancylostoma caninum with low-level resistance (isolate NT) and high-level resistance (isolate PR) to pyrantel to nicotinic agonist drugs reported to be selective for three nAchR subtypes. We used larval motility and conformation assays and force transduction experiments with adult worms. Pyrantel and levamisole were less potent against larvae of isolate PR than larvae of isolate NT (up to an 18-fold increase in the 50% inhibitory concentration); on the other hand, bephenium was more potent against larvae of isolate PR than larvae of isolate NT (twofold) and nicotine had the same potency against larvae of both isolates. In adults, pyrantel, levamisole, and nicotine were less potent against isolate PR than isolate NT (two- to threefold), but the potency of bephenium against the two isolates was equivalent. Our data indicate a complex pattern of nAchRs in this species and suggest that the two isolates differ in their relative sensitivities to agonists targeting different nAchRs.

Inactivation of chloramphenicol by Gram-negative microorganisms

1968 ◽  
Vol 14 (8) ◽  
pp. 891-899 ◽  
Author(s):  
David Sompolinsky ◽  
Ruth Ziegler-Schlomowitz ◽  
Dora Herczog
Keyword(s):  
Escherichia Coli ◽  
Growth Medium ◽  
Minimal Medium ◽  
Resistance Factor ◽  
The Other ◽  
Gram Negative ◽  
Resistant Strains ◽  
Gram Negative Organisms ◽  
High Level ◽  
Level Resistance

Two derivative strains of Escherichia coli with high-level resistance to chloramphenicol, one carrying an episomal resistance factor and the other a chromosomal mutant, were both shown to be potent inactivators of the drug. When 1 mM chloramphenicol was added to an exponential culture in minimal medium, growth was halted until 85–90% of the drug was inactivated by acylation. At this state the drug was essentially monoacylated. During and after growth, esterification of the second alcoholic group occurred, though at a slower rate. Arylamines, in amounts up to 10% of chloramphenicol equivalents, were demonstrated in the growth medium after 1–3 days' incubation.With an acetateless mutant of Escherichia coli K12, carrying a resistance factor, it was shown that 5–6 moles of acetate was consumed for every mole of chloramphenicol acylated.Inactivation of chloramphenicol by Gram-negative organisms from infections in hospitalized patients was also examined. Among 103 strains susceptible to chloramphenicol, none produced considerable amounts of chloramphenicol esters. The same was the case with 14 resistant strains of Pseudomonas. Of 134 other resistant organisms examined, including strains of Escherichia, Proteus, Klebsiella, Salmonella, and Shigella, 133 were producers of chloramphenicol esters, and in most cases the drug was partly or entirely diacylated.

scholarly journals Extreme Environments and High-Level Bacterial Tellurite Resistance

2019 ◽  
Vol 7 (12) ◽  
pp. 601 ◽  
Author(s):  
Chris Maltman ◽  
Vladimir Yurkov
Keyword(s):  
Extreme Environments ◽  
Pollutant Removal ◽  
The Other ◽  
Tellurite Resistance ◽  
Elemental Tellurium ◽  
E Coli ◽  
Resistance Reduction ◽  
High Level ◽  
The Impact ◽  
Level Resistance

Bacteria have long been known to possess resistance to the highly toxic oxyanion tellurite, most commonly though reduction to elemental tellurium. However, the majority of research has focused on the impact of this compound on microbes, namely E. coli, which have a very low level of resistance. Very little has been done regarding bacteria on the other end of the spectrum, with three to four orders of magnitude greater resistance than E. coli. With more focus on ecologically-friendly methods of pollutant removal, the use of bacteria for tellurite remediation, and possibly recovery, further highlights the importance of better understanding the effect on microbes, and approaches for resistance/reduction. The goal of this review is to compile current research on bacterial tellurite resistance, with a focus on high-level resistance by bacteria inhabiting extreme environments.

scholarly journals Evidence that there are two types of determinant for tetracycline resistance among R-factors

1978 ◽  
Vol 31 (1) ◽  
pp. 75-84 ◽  
Author(s):  
E. C. R. Reeve
Keyword(s):  
Growth Rate ◽  
Host Cell ◽  
Resistance Gene ◽  
Tetracycline Resistance ◽  
Repressor Gene ◽  
Homologous Group ◽  
R Factor ◽  
High Level ◽  
R Factors ◽  
Level Resistance

SUMMARYA series of derepressed mutants of the tetracycline resistance (T) determinant in R-factor R57 have been found to be repressor-negative and recessive to the T determinant in R6. It is shown that these (Tdr) mutants are dominant to the inducible T determinant in RPl, indicating that the T determinants in R57 and RP1 code for different repressors of the resistance gene. The same Tdr determinants are unstable in cells carrying both the R57 mutant and RP1, probably due to selection against the dominant Tdr gene because it depresses the growth rate of the host cell compared with its T+homologue. It is suggested that the T determinants giving high-level resistance in R57, R6 and R100 form one homologous group, probably disseminated by the transposon TnlO, while T determinants giving a much lower level of resistance, such as that in RP1, form a separate group, which may include those in R46, and R199. It is proposed that the gene responsible for tetracycline resistance should be designatedtetAand the repressor genetetI. The R57 Tdr mutants then have the genotypetetI−tetA+.

scholarly journals High-Level Resistance to Trimethoprim in Clinical Isolates of Campylobacter jejuni by Acquisition of Foreign Genes (dfr1 and dfr9) Expressing Drug-Insensitive Dihydrofolate Reductases

1998 ◽  
Vol 42 (12) ◽  
pp. 3059-3064 ◽  
Author(s):  
Amera Gibreel ◽  
Ola Sköld
Keyword(s):  
Campylobacter Jejuni ◽  
Resistance Genes ◽  
The Other ◽  
Clinical Isolates ◽  
Resistance Level ◽  
Dihydrofolate Reductases ◽  
Foreign Genes ◽  
The Right ◽  
High Level ◽  
Level Resistance

ABSTRACT The pathogenic bacterium Campylobacter jejuni has been regarded as endogenously resistant to trimethoprim. The genetic basis of this resistance was characterized in two collections of clinical isolates of C. jejuni obtained from two different parts of Sweden. The majority of these isolates were found to carry foreigndfr genes coding for resistant variants of the dihydrofolate reductase enzyme, the target of trimethoprim. The resistance genes, found on the chromosome, were dfr1 anddfr9. In about 10% of the strains, the dfr1and dfr9 genes occurred simultaneously. About 10% of the examined isolates were found to be negative for these dfrgenes and showed a markedly lower trimethoprim resistance level than the other isolates. The dfr9 and dfr1 genes were located in the context of remnants of a transposon and an integron, respectively. Two different surroundings for thedfr9 gene were characterized. One was identical to the right-hand end of the transposon Tn5393, and in the other, the dfr9 gene was flanked by only a few nucleotides of a Tn5393 sequence. The insertion of the dfr9 gene into the C. jejuni chromosome could have been mediated by Tn5393. The frequent occurrence of high-level trimethoprim resistance in clinical isolates of C. jejuni could be related to the heavy exposure of food animals to antibacterial drugs, which could lead to the acquisition of foreign resistance genes in naturally transformable strains of C. jejuni.

scholarly journals Mutation in Serratia marcescens AmpC β-Lactamase Producing High-Level Resistance to Ceftazidime and Cefpirome

2001 ◽  
Vol 45 (8) ◽  
pp. 2331-2339 ◽  
Author(s):  
Alessandro Raimondi ◽  
Francesca Sisto ◽  
Hiroshi Nikaido
Keyword(s):  
Serratia Marcescens ◽  
Catalytic Efficiency ◽  
Fold Increase ◽  
Mutant Enzyme ◽  
Kinetic Properties ◽  
Cloning And Sequencing ◽  
Mutant Strains ◽  
High Level ◽  
Outer Membrane Permeability ◽  
Level Resistance

ABSTRACT Starting from a clinical isolate of Serratia marcescens that produced a chromosomally encoded AmpC β-lactamase inducibly, we isolated by stepwise selection two laboratory mutants that showed high levels of resistance to some cephalosporins. The 98R mutant apparently overproduced the unaltered β-lactamase constitutively, but the 520R mutant produced an altered enzyme, also constitutively. Ceftazidime and cefpirome MICs for the 520R mutant were much higher (512 and 64 μg/ml, respectively) than those for the 98R mutant (16 and 16 μg/ml, respectively). Yet the MICs of cephaloridine and piperacillin for the 520R mutant were four- to eightfold lower than those for the 98R mutant. Cloning and sequencing of theampC alleles showed that in the 520R mutant enzyme, the Thr64 residue, about two turns away from the active-site serine, was mutated to isoleucine. This resulted in a >1,000-fold increase in the catalytic efficiency (k cat/K m ) of the mutated AmpC enzyme toward ceftazidime, whereas there was a >10-fold decrease in the efficiency of the mutant enzyme toward cefazolin and cephaloridine. The outer membrane permeability of the 520R strain to cephalosporins was also less than in the 98R strain, and the alteration of the kinetic properties of the AmpC enzyme together with this difference in permeability explained quantitatively the resistance levels of both mutant strains to most agents studied.

scholarly journals Generation and characterisation of P. falciparum parasites with a G358S mutation in the PfATP4 Na+ pump and clinically relevant levels of resistance to some PfATP4 inhibitors

2022 ◽  
Author(s):  
Deyun Qiu ◽  
Jinxin V. Pei ◽  
James E. O. Rosling ◽  
Dongdi Li ◽  
Yi Xue ◽  
...  
Keyword(s):  
Growth Rate ◽  
Clinical Trials ◽  
Inhibitory Concentration ◽  
Phase 1 ◽  
Clinical Development ◽  
Parasite Growth ◽  
Clinically Significant ◽  
Moderate Resistance ◽  
High Level ◽  
Level Resistance

Small-molecule inhibitors of PfATP4, a Plasmodium falciparum protein that is believed to pump Na+ out of the parasite while importing H+, are on track to become much-needed new antimalarial drugs. The spiroindolone cipargamin is poised to become the first PfATP4 inhibitor to reach the field, having performed strongly in Phase 1 and 2 clinical trials. Previous attempts to generate cipargamin-resistant parasites in the laboratory have yielded parasites with reduced susceptibility to the drug; however, the highest 50% inhibitory concentration reported to date is 24 nM. Here, we show that P. falciparum parasites can acquire a clinically-significant level of resistance to cipargamin that enables them to withstand micromolar concentrations of the drug. Independent experiments to generate high-level cipargamin resistance using different protocols and strains led to the same change each time - a G358S mutation in PfATP4. Parasites with this mutation showed high-level resistance not only to cipargamin, but also to the dihydroisoquinolone (+)-SJ733. However, for certain other (less clinically advanced) PfATP4-associated compounds the G358S mutation in PfATP4 conferred only moderate resistance or no resistance. The G358S mutation in PfATP4 did not affect parasite susceptibility to antimalarials that do not target PfATP4. The G358S mutation in PfATP4, and the equivalent mutation in the Toxoplasma gondii ATP4 homologue (G419S), decreased the sensitivity of the Na+-ATPase activity of ATP4 to inhibition by cipargamin and (+)-SJ733, and decreased the sensitivity of parasites expressing these ATP4 mutations to disruption of parasite Na+ regulation by cipargamin- and (+)-SJ733. The G358S mutation in PfATP4 reduced the affinity of the protein for Na+ and was associated with an increase in the parasite's resting cytosolic Na+ concentration; however, no significant defect in parasite growth rate was observed. Our findings suggest that codon 358 in pfatp4 should be monitored closely in the field as a molecular marker for cipargamin resistance, and that PfATP4 inhibitors in clinical development should be tested for their activity against PfATP4G358S parasites.

scholarly journals Description of Two New Isolates ofStreptococcus pneumoniae in Spain That Are Highly Resistant to Cefotaxime

1998 ◽  
Vol 42 (10) ◽  
pp. 2768-2769 ◽  
Author(s):  
Joaquín Ruiz ◽  
Marco Sempere ◽  
Encarnación Simarro ◽  
Asunción Fenoll
Keyword(s):  
Streptococcus Pneumoniae ◽  
The Other ◽  
Resistance To Penicillin ◽  
High Level ◽  
Level Resistance

Two strains of Streptococcus pneumoniae isolated from sputum and bronchoalveolar samples with high-level resistance to cefotaxime (MIC = 8 to 16 μg/ml) are described. One of them, belonging to serogroup 19, was also highly resistant to penicillin (MIC = 16 μg/ml), while the other, of serogroup 14, was intermediate in its resistance to penicillin (MIC = 0.25 μg/ml). To our knowledge, these are the first two strains to be isolated in Spain with such high levels of resistance to cefotaxime.

scholarly journals Biological Cost of AmpC Production forSalmonella enterica Serotype Typhimurium

2000 ◽  
Vol 44 (11) ◽  
pp. 3137-3143 ◽  
Author(s):  
M. I. Morosini ◽  
J. A. Ayala ◽  
F. Baquero ◽  
J. L. Martínez ◽  
J. Blázquez
Keyword(s):  
Growth Rate ◽  
Regulatory Gene ◽  
Striking Feature ◽  
Gene Encoding ◽  
Gram Negative ◽  
Resistance Phenotype ◽  
Biological Cost ◽  
High Level ◽  
Horizontal Acquisition ◽  
Level Resistance

ABSTRACT Chromosomally mediated AmpC-type β-lactamases are frequently found among Enterobacteriaceae. Hyperproduction of AmpC β-lactamase results in high-level resistance to β-lactam antibiotics. One striking feature of Salmonella is the absence of the structural ampC gene, encoding AmpC β-lactamase, in contrast with other members in theEnterobacteriaceae family, such as Escherichia,Citrobacter, or Enterobacter. The horizontal acquisition of ampC genes is one of the causes of the increased resistance to extended-spectrum cephalosporins and β-lactamase inhibitors among gram-negative rods. Nevertheless, despite the high number of β-lactam-resistant Salmonellaisolates so far described, only two strains expressing resistance to cephalosporin and β-lactamase inhibitors which is mediated by AmpC-type enzymes have been found. In this work, data are provided which support the possibility that the maintenance and expression of the ampC gene may represent an unbearable cost forSalmonella in terms of reduction of some of its lifestyle attributes, such as growth rate and invasiveness. The deleterious AmpC burden can be eliminated by decreasing the production of AmpC when both the regulatory gene, ampR, and ampC are present in Salmonella. Thus, it is suggested that the two genes have to be acquired together by Salmonella, leading to an inducible β-lactam resistance phenotype. AmpC synthesis did not produce major variations in the peptidoglycan composition ofSalmonella.

High-level resistance to oxidative stress in Lactococcus lactis conferred by Bacillus subtilis catalase KatE

Microbiology ◽  
2005 ◽  
Vol 151 (9) ◽  
pp. 3011-3018 ◽  
Author(s):  
T. Rochat ◽  
A. Miyoshi ◽  
J. J. Gratadoux ◽  
P. Duwat ◽  
S. Sourice ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bacillus Subtilis ◽  
Lactococcus Lactis ◽  
Fold Increase ◽  
Inducible Promoter ◽  
Optimization Strategy ◽  
High Level ◽  
The Impact ◽  
Level Resistance

Lactococcus lactis, a lactic acid bacterium widely used for food fermentations, is often exposed to damaging stress conditions. In particular, oxidative stress leads to DNA, protein and membrane damages that can be lethal. As L. lactis has no catalase, the impact of production of the Bacillus subtilis haem catalase KatE on its oxidative stress resistance was tested. This cytoplasmic catalase was engineered for extracellular expression in L. lactis with an optimization strategy based on fusion to the nisin-inducible promoter and a lactococcal signal peptide (SPUsp45). The production of KatE by L. lactis conferred an 800-fold increase in survival after 1 h exposure to 4 mM hydrogen peroxide, and a 160-fold greater survival in long-term (3 days) survival of aerated cultures in a cydA mutant, which is unable to respire. The presence of KatE protected DNA from oxidative damage and limited its degradation after long-term aeration in a cydA/recA mutant, defective in DNA repair. L. lactis is thus able to produce active catalase that can provide efficient antioxidant activity.

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