Mobile colistin resistance (mcr) genes were described recently in Gram-negative bacteria including carbapenem-resistant Enterobacterales. There are ten mcr genes described in different Gram-negative ...bacteria, however, Escherichia coli harboring mcr-1 gene is by far the most frequent combination. In Argentina, mcr-1 gene was characterized only on plasmids belonging to IncI2 group. The aim of this work was to get new insights of mcr-1-harboring plasmids from E. coli. Eight E. coli isolates from a larger collection of 192 clinical E. coli isolates carrying the mcr-1 gene were sequenced using next generation technologies. Three isolates belonged to ST131 high-risk clone, and five to single ST, ST38, ST46, ST226, ST224, and ST405. Eight diverse mcr-1-harboring plasmids were analyzed: IncI2 (1), IncX4 (3), IncHI2/2A (3) and a hybrid IncFIA/HI1A/HI1B (1) plasmid. Plasmids belonging to the IncI2 (n = 1) and IncX4 (n = 3) groups showed high similarity with previously described plasmids. Two IncHI2/HI2A plasmids, showed high identity between them, while the third, showed several differences including additional resistance genes like tet(A) and floR. One IncFIA/H1A/H1B hybrid plasmid was characterized, highly similar to pSRC27-H, a prototype plasmid lacking mcr genes. mcr-1.5 variant was found in four plasmids with three different Inc groups: IncI2, IncHI2/HI2A and the hybrid FIA/HI1A/HI1B plasmid. mcr-1.5 variant is almost exclusively described in our country and with a high frequency. In addition, six E. coli isolates carried three allelic variants codifying for CTX-M-type extended-spectrum-β-lactamases: blaCTX-M-2 (3), blaCTX-M-65 (2), and blaCTX-M-14 (1). It is the first description of mcr-1 harboring plasmids different to IncI2 group in our country. These results represents new insights about mcr-1 harboring plasmids recovered from E. coli human samples from Argentina, showing different plasmid backbones and resistance gene combinations.
The extensively drug-resistant NDM-1-producing Klebsiella quasipneumoniae subsp. quasipneumoniae M17277 (Kqsq-M17277) was only susceptible to colistin and fosfomycin. Whole genome sequencing of ...Kqsq-M17277 was performed through Illumina (short reads) and Oxford Nanopore Technologies (long reads). Hybrid assembly of short and long reads rendered circular contigs of the Kqsq-M17277 chromosome and three plasmids of 477,340 (p17277A_477), 138,998 (p17277C_138, which harbored blaNDM-1) and 123,307 bp (p17277B_123). In silico analysis showed that p17277A_477 was not previously described, belonged to the IncHI2 incompatibility group and contained 51 complete or partial (≥300 bp) insertion sequences and Tn3 family transposons, which encompassed, as a whole, 14% of the p17277A_477 sequence. In silico search for antimicrobial resistance genes revealed that p17277A_477 harbored the recently described plasmid-encoded mcr-9 gene (colistin resistance), besides other resistance genes. This is the first worldwide report of a K. quasipneumoniae harboring mcr-9 and blaNDM-1 and the first report of mcr-9 in Latin America. This gene was embedded in a genetic structure, i.e., IS903B-like/mcr-9/wbuC/IS26, that was found in 71% of the mcr-9-harboring sequences of the NCBI Nucleotide Collection database. The qseC and qseB genes involved in mcr-9 expression were not found in Kqsq-M17277, which could explain its colistin susceptibility. Fifteen additional resistance genes were detected in p17277A_477. Ten of them aac(6′)-IIc, aadA2, aph(3′)-Ia, blaDHA-1, dfrA12, ereA2, mphA, qnrB4, sul1 and tet(D) were found clustered within a 44,907-bp-long array of IS26-bounded resistance genes. The plasmid-mediated quinolone resistance gene qnrB4 was located in a complex class 1 integron within this IS26-bounded resistance gene cluster. p17277A_477 was self-transferable by conjugation to Escherichia coli J53, azide-resistant. The Tra1 and Tra2 conjugative transfer regions of the IncHI2 plasmid R478 were found by in silico search. p17277A_477 is a complex plasmid that provides a large baggage of both resistance genes and genetic resources for plasmid rearrangements and additional resistance gene acquisition.
•mcr-9 is present in a NDM-1-producing K. quasipneumoniae.•First report of mcr-9 in Latin America.•mcr-9 is harbored in a 477,340-bp conjugative IncHI2 plasmid (p17277A_477).•mcr-9 was embedded in the IS903B-like/mcr-9/wbuC/IS26 structure.•p17277A_477 contains an IS26-bounded resistance gene cluster.
We have characterized nine mcr-1-harboring plasmids from clinical Escherichia coli isolates previously described in Argentina and Canada. Three of these plasmids carried a mcr-1-variant called here ...mcr-1.5. All these E. coli isolates were not clonally related and were recovered in different years and locations. However, their mcr-1-harboring plasmids showed high identity among them and to others characterized in other countries, which strongly suggests that this plasmid-type is playing an important role in spreading this mechanism of resistance to polymyxins.
Colistin is a polymyxin antibiotic (polymyxin E) that has in recent years re-emerged as an option for treatment of multidrug-resistant bacteria. Recently, the re-introduction of colistin resulted in ...the appearance of colistin-resistant bacteria, which is usually caused by LPS modifications. The fact that this modification is mediated by a plasmid carrying the mcr-1 gene, implies a horizontal transfer of colistin resistance. In Argentina, the National Reference Laboratory in Antimicrobial Resistance (NRLAR), has recently screened several bacteria for the MCR-1 plasmid, detecting nine
Escherichia coli
isolates carrying the plasmid with the mcr-1 gene, among others. In this context, we proposed to assess the effect of surface charge modifications induced by the plasmid MCR-1 and its impact on the resulting colistin resistance in two clinical isolates of colistin-resistant
E. coli
. Using zeta potential assays, we confirmed the reduction of negative charge exposure on clinical isolates compared to the reference strain of
E. coli
. In addition, through permeabilization assays, we were able to correlate this reduction in charge exposure with the extent of damage to the bacterial membrane. The fact that this surface charge modification through substitution of lipid A is plasmid encoded, represents an important concern for future antimicrobial peptide drug development.
Antibiotic resistance is one of the main problems concerning public health or clinical practice. Antimicrobial peptides appear as good candidates for the development of new therapeutic drugs. In this ...study we de novo designed a group of cationic antimicrobial peptides, analyzed its physicochemical properties, including its structure by circular dichroism and studied its antimicrobial properties against a panel of clinical isolates expressing different mechanisms of resistance. Three cationic alpha helical peptides exhibited antimicrobial activity comparable to, or even better than the comparator omiganan (MBI-226).
De novo designed alpha helical cationic peptides with antimicrobial activity against multi-resistant clinical isolates. Display omitted
•De novo designed cationic peptides.•Physicochemical properties of peptides.•Antimicrobial resistant bacteria.
Antimicrobial resistance is considered one of the most critical threat for both human and animal health. Recently, reports of infection or colonization by carbapenemase-producing Enterobacterales in ...companion animals had been described. This study report the first molecular characterization of NDM-producing Enterobacterales causing infections in companion animals from Argentina. Nineteen out of 3662 Enterobacterales isolates analyzed between October 2021 and July 2022 were resistant to carbapenemes by VITEK2C and disk diffusion method, and suspected to be carbapenemase-producers. Ten isolates were recovered from canine and nine from feline animals. Isolates were identified as K. pneumoniae (n = 9), E. coli (n = 6) and E. cloacae complex (n = 4), and all of them presented positive synergy among EDTA and carbapenems disks, mCIM/eCIM indicative of metallo-carbapenemase production and were also positive by PCR for bla
gene. NDM variants were determined by Sanger sequencing method. All 19 isolates were resistant to β-lactams and aminoglycosides but remained susceptible to colistin (100%), tigecycline (95%), fosfomycin (84%), nitrofurantoin (63%), minocycline (58%), chloramphenicol (42%), doxycycline (21%), enrofloxacin (5%), ciprofloxacin (5%) and trimethoprim/sulfamethoxazole (5%). Almost all isolates (17/19) co-harbored bla
plus bla
, one harbored bla
alone and the remaining bla
. E. coli and E. cloacae complex isolates harbored bla
or bla
groups, while all K. pneumoniae harbored only bla
genes. All E. coli and E. cloacae complex isolates harbored bla
, while in K. pneumoniae bla
(n = 6), bla
(n = 2), and bla
plus bla
(n = 1) were confirmed. MLST analysis revealed the following sequence types by species, K. pneumoniae: ST15 (n = 5), ST273 (n = 2), ST11, and ST29; E. coli: ST162 (n = 3), ST457, ST224, and ST1196; E. cloacae complex: ST171, ST286, ST544 and ST61. To the best of our knowledge, this is the first description of NDM-producing E. cloacae complex isolates recovered from cats. Even though different species and clones were observed, it is remarkable the finding of some major clones among K. pneumoniae and E. coli, as well as the circulation of NDM as the main carbapenemase. Surveillance in companion pets is needed to detect the spread of carbapenem-resistant Enterobacterales and to alert about the dissemination of these pathogens among pets and humans.
Background and Aim: Salmonellosis is one of the most common foodborne diseases in the world, and the increasing antibiotic resistance in Salmonella enterica subsp. enterica recovered from food ...animals constitutes an important risk from a One Health approach. This study aimed to characterize antibiotic resistance and some of its associated resistance determinants in different S. enterica serovars isolated from pigs in Argentina.
Materials and Methods: A retrospective study was conducted on Salmonella strains isolated between 2011 and 2015 from pigs in the Pampean region of Argentina. The antimicrobial susceptibility patterns to 21 antimicrobials and some antibiotic resistance determinants were characterized in 55 Salmonella isolates, representing 58 farms.
Results: We identified 56% (n=30) of the strains as multidrug-resistant, where resistance to tetracycline (62%, n=34), ampicillin (53%, n=29), nalidixic acid (53%, n=29), chloramphenicol (33%, n=18), and trimethoprim-sulfamethoxazole (31%, n=17) was most common. The wide range of resistance to ampicillin correlates with the presence of TEM type β-lactamases in the strains. However, high susceptibility was found in the new generation of β-lactams. Fluoroquinolone resistance is a major concern. Most strains with decreased susceptibility to ciprofloxacin showed gyrA mutations and plasmid-mediated quinolone resistance gene qnrB.
Conclusion: Here, we identified broad resistance to some antibiotics frequently used in human therapeutics and several easily transferable resistance mechanisms that could endanger public health.
Multidrug-resistant
emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting ...histories of the antibiotic-resistant
lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn
-type and Tn
-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly sampled Tn
-type insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence, selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.
The
gene is an important candidate in pharmacogenetic studies of antipsychotic-induced weight gain (AIWG). However, inconsistent results have been obtained. The present study investigated the ...association between -759C>T, functional polymorphism of the
receptor, and AIWG.
A prospective cohort of 48 female inpatients with schizophrenia and related illness treated according to normal clinical practice with second generation antipsychotics (SGAs) risperidone, clozapine, quetiapine, and olanzapine were evaluated. Patients were weighted at admission and again at 6 weeks of hospitalization. Weight gain was defined as an increase≥7% of baseline weight. The association between polymorphisms
and weight gain was evaluated. Multiple logistic regression was run to determine potential confounders.
Patients with the T allele at position -759 (TT or CT) gained less weight as compared to patients who did not have the allele. This association was not affected by possible confounding factors such as age, baseline BMI, and prior psychopharmacological treatment.
The T allele at position -759 protects against AIWG in female patients with schizophrenia.
The aim of this study was to characterize the first 14 optrA-carrying linezolid resistant E. faecalis clinical isolates recovered in seven Argentinian hospitals between 2016 and 2021. The ...epidemiology of optrA-carrying isolates and the optrA genetic context were determined.
The isolates were phenotypically and genotypically characterized. Susceptibility to 13 antimicrobial agents was performed; clonal relationship was assessed by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Data provided by the whole-genome sequencing were used for identification of sequence types, antimicrobial resistance genes, optrA variants, phylogenetic tree, and mobile genetic elements responsible to the dissemination of these strains.
All the optrA-carrying E. faecalis isolates were multidrug-resistant and harboured several antimicrobial resistance genes. They carried three optrA variants and belonged to different lineages; however, three of them belonged to the hyperepidemic CC16. Mobile genetic elements were detected in all the isolates. The analysis of the optrA flanking region suggests the plasmidic localization in most of the isolates.
To the best of our knowledge, this is the first report of optrA-mediated linezolid resistance in Argentina. The emergence and dissemination of the optrA genes in clinical E. faecalis isolates are of concern and highlights the importance of initiating the antimicrobial surveillance of Enterococcus spp. under a One Health strategy.
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