Biology subjects

Corso, A.

Publications and source records attributed to Corso, A..

5 recordsLinked to original sources

bioRxiv2025

Emerging Resistance to Novel -βLactam β-Lactamase Inhibitor Combinations in Klebsiella pneumoniae bearing KPC Variants

BackgroundKlebsiella pneumoniae carbapenemase (KPC) variants, predominantly KPC-2 and KPC-3, are significant global resistance mechanisms. KPC-2 and KPC-3 confer resistance to a broad range of {beta}-lactams, including carbapenems, while remaining susceptible to ceftazidime-avibactam (CZA). Recently, new KPC variants have developed resistance to CZA through mutations, insertions, or deletions in regions such as the {Omega}-loop, 240-loop (237-243 aa), and 270-loop (266-275 aa). This study aimed to investigate the collateral resistance to cefiderocol (FDC) and cefepime/zidebactam (FPZ) among isolates with these mutations. MethodsFifteen clinical isolates of KPC-producing Klebsiella spp. were analyzed, representing 15 distinct variants. Antimicrobial susceptibility testing determined the MICs for CZA, carbapenems, FDC, FPZ, and other antibiotics. Synergy between CZA and FDC was assessed. Whole-genome sequencing (WGS) was used to identify mutations contributing to resistance. ResultsCZA resistance was confirmed in 12 of the 15 KPC variants. Collateral resistance to FDC was observed in eight isolates, with five exhibiting spontaneous resistant subpopulations. Six FDC-resistant strains had mutations in the 270-loop (266-275 aa). Collateral resistance to FPZ was seen in three KPC variants, especially those with mutations in the 270-loop (266-275 aa), though many {Omega}-loop and 240-loop (237-243 aa) mutants remained susceptible. WGS of FDC-resistant subpopulations revealed additional mutations in ompC, rpoC, dksA, and cirA. ConclusionsThis study demonstrates that emerging KPC variants showing resistance to CZA also exhibit resistance to FDC, with collateral resistance to FPZ observed to a lesser extent. Identifying mutations in blaKPC, cirA, and other genes is important to understand resistance mechanisms for effective therapies.

microbiology↗

bioRxiv2024

Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp.

The emergence of Gram-negative bacteria resistant to multiple antibiotics, particularly carbapenem-resistant (CR) Acinetobacter strains, poses a significant threat globally. Despite efforts to develop new antimicrobial therapies, limited progress has been made, with only two drugs--cefiderocol and sulbactam-durlobactam--showing promise for CR-Acinetobacter infections. Cefiderocol, a siderophore cephalosporin, demonstrates promising efficacy in the treatment of Gram-negative infections. However, resistance to cefiderocol has been reported in A. baumannii. Combination therapies, such as cefiderocol with avibactam or sulbactam, show reduced MICs against cefiderocol-non-susceptible strains with in vivo efficacy, although the outcomes can be complex and species-specific. In the present work, the molecular characterization of spontaneous cefiderocol-resistant variants, a CRAB strain displaying antagonism with sulbactam and an A. lwoffii strain showing antagonism with avibactam, were studied. The results reveal intriguing insights into the underlying mechanisms, including mutations affecting efflux pumps, transcriptional regulators, and iron homeostasis genes. Moreover, gene expression analysis reveals significant alterations in outer membrane proteins, iron homeostasis, and {beta}-lactamases, suggesting adaptive responses to selective pressure. Understanding these mechanisms is crucial for optimizing treatment strategies and preventing adverse clinical outcomes. This study highlights the importance of preemptively assessing drug synergies to navigate the challenges posed by antimicrobial resistance in CR-Acinetobacter infections.

microbiology↗

bioRxiv2021

Impact of Human Serum Proteins on Susceptibility of Acinetobacter baumannii to Cefiderocol: role of iron transport

Cefiderocol is a siderophore antibiotic that co-opts iron transporters to facilitate cell entry. We show that genes related to iron uptake systems and resistance to {beta}-lactams in Acinetobacter baumannii have altered expression levels in the presence of human serum, human serum albumin, or human pleural fluid. Cefiderocol MICs are also raised in the presence of the mentioned fluids. Clinical response in A. baumannii infections may be related to the interplay of these human factors.

microbiology↗

bioRxiv2020

Pseudomonas putida group species serve as reservoirs of conjugative plasmids disseminating Tn402-like class 1 integrons carrying blaVIM-2 metallo-β-lactamase genes

The Pseudomonas putida group (P. putida G) is composed of at least 21 species associated to a wide range of environments, including the clinical setting. Here, we characterized 13 carbapenem-resistant P. putida G clinical isolates carrying blaVIM-2 from different hospitals of Argentina. Multilocus sequencing (MLSA) and phylogenetic analyses based on the 16S rDNA, gyrB and rpoD sequences comparison allowed us to assign them to 7 well-differentiated species. Sequencing analysis revealed that blaVIM-2 genes were carried in these isolates by three different class 1 integrons (In41, In899 and In528) embedded into Tn402-like transposons. Those harboring In41 and In899 were designated Tn6335 and Tn6336, respectively, with the former found among 10 isolates. Both encompassed complete transposition modules and inverted repeats boundaries characteristic of the Tn5053/Tn402 family, whereas the third, bearing In528, exhibited a defective tni module. Tn6335 and Tn6336 were located in conjugative pLD209-type plasmids in P. asiatica, P. juntendi, P. putida G/II, and P. putida G/V isolates, and could be mobilized to Escherichia coli and P. aeruginosa indicating a relevant mechanism of blaVIM-2 dissemination. In other P. asiatica and P. putida G/II isolates, Tn6335 was found inserted into the Tn21 subgroup transposons-res region, indicating capability for intragenomic mobilization and further dissemination associated to Tn3 family transposons. The Tn402-like defective element was also found inserted into the res region of another Tn3 family transposon in a P. monteilii isolate, but in an atypical orientation. Overall findings shed light on the mechanisms by which resistance genes move through environmental and opportunist Pseudomonas species.

microbiology↗

bioRxiv2020

Italian Odonates in the Pandora's Box: A Comprehensive DNA Barcoding Inventory Shows Taxonomic Warnings at the Holarctic Scale

The Odonata are considered among the most endangered freshwater faunal taxa. Their DNA-based monitoring relies on validated reference datasets that are often lacking or do not cover important biogeographical centres of diversification. This study presents the results of a DNA barcoding campaign on Odonata, based on the standard 658 bp 5 end region of the mitochondrial COI gene, involving the collection of 812 specimens (409 of which barcoded) from peninsular Italy and its main islands (328 localities), belonging to all the 88 species (31 Zygoptera and 57 Anisoptera) known from the country. Additional BOLD and GenBank data from Holarctic samples expanded the dataset to 1294 DNA barcodes. A multi-approach species delimitation analysis involving two distance (OT and ABGD) and four tree-based (PTP, MPTP, GMYC, bGMYC) methods were used to explore these data. Of the 88 investigated morphospecies, 75 (85%) unequivocally corresponded to distinct Molecular Operational Units, whereas the remaining ones were classified as warnings (i.e., showing a mismatch between morphospecies assignment and DNA-based species delimitation). These results are in contrast with other DNA barcoding studies on Odonata showing up to 95% of identification success. The species causing warnings were grouped in three categories depending on if they showed low, high, or mixed genetic divergence patterns. The analysis of haplotype networks revealed unexpected intraspecific complexity at the Italian, Palearctic, and Holarctic scale, possibly indicating the occurrence of cryptic species. Overall, this study provides new insights into the taxonomy of odonates and a valuable basis for future DNA and eDNA-based monitoring studies.

zoology↗