(FBIOyF) Departamento de Bioquímica Clínica - Artículos

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https://rephip.unr.edu.ar/handle/2133/2569

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The H-NS regulator plays a role in the stress induced by carbapenemase expression in acinetobacter baumannii
(American Society for Microbiology, 2020-08-26) Huang, Fanny; Fitchett, Noelle; Razo Gutierrez, Chelsea; Le, Casin; Martinez, Jasmine; Ra, Grace; López, Carolina; González, Lisandro J.; Sieira, Rodrigo; Vila, Alejandro J.; Bonomo, Robert A.; Ramírez, María Soledad; https://orcid.org/0000-0002-9904-7890
Disruption of the histone-like nucleoid structuring protein (H-NS) was shown to affect the ability of Gram-negative bacteria to regulate genes associated with virulence, persistence, stress response, quorum sensing, biosynthesis pathways, and cell adhesion. Here, we used the expression of metallo--lactamases (MBLs), known to elicit envelope stress by the accumulation of toxic precursors in the periplasm, to interrogate the role of H-NS in Acinetobacter baumannii, together with other stressors. Using a multidrug-resistant A. baumannii strain, we observed that H-NS plays a role in alleviating the stress triggered by MBL toxic precursors and counteracts the effect of DNA-damaging agents, supporting its role in stress response.
Acceso Abierto
Structural determinants of Arabidopsis thaliana Hyponastic Leaves 1 function in vivo
(Public Library of Science, 2014-11-19) Burdisso, Paula; Milia, Fernando; Schapire, Arnaldo L.; Bologna, Nicolás G.; Palatnik, Javier F.; Rasia, Rodolfo M.
MicroRNAs have turned out to be important regulators of gene expression. These molecules originate from longer transcripts that are processed by ribonuclease III (RNAse III) enzymes. Dicer proteins are essential RNAse III enzymes that are involved in the generation of microRNAs (miRNAs) and other small RNAs. The correct function of Dicer relies on the participation of accessory dsRNA binding proteins, the exact function of which is not well-understood so far. In plants, the double stranded RNA binding protein Hyponastic Leaves 1 (HYL1) helps Dicer Like protein (DCL1) to achieve an efficient and precise excision of the miRNAs from their primary precursors. Here we dissected the regions of HYL1 that are essential for its function in Arabidopsis thaliana plant model. We generated mutant forms of the protein that retain their structure but affect its RNA-binding properties. The mutant versions of HYL1 were studied both in vitro and in vivo, and we were able to identify essential aminoacids/residues for its activity. Remarkably, mutation and even ablation of one of the purportedly main RNA binding determinants does not give rise to any major disturbances in the function of the protein. We studied the function of the mutant forms in vivo, establishing a direct correlation between affinity for the pri-miRNA precursors and protein activity.
Acceso Abierto
Acute diarrhoea in children: determination of duration using a combined bismuth hydroxide gel and oral rehydration solution therapy vs. oral rehydration solution
(MDPI, 2016-12-21) Oviedo, Adriana; Díaz, Mirna; Valenzuela, María Laura; Vidal, Victoria; Racca, Liliana; Bottai, Hebe; Priore, Graciela; Peluffo, Graciela; Di Bartolomeo, Susana; Cabral, Graciela; Toca, María del Carmen
Oral rehydration salt (ORS) treatment in young children with acute diarrhoea (AD) has contributed to decrease mortality associated with dehydration although effective strategies to reduce morbidity associated with this disease are required. The aim of this study was to evaluate the diarrhoea duration when using combined colloidal bismuth hydroxide gel (CBHG) and oral rehydration salt treatment compared with ORS therapy in children with AD. We designed a double-blind, randomised prospective study with treatment and control groups. Patients aged one to 12 years, with no prior pathology and with AD of less than 48 h were included. The Chi-squared and Mann-Whitney tests were used, as well as the Cox proportional hazards model and the Kaplan-Meier estimator. Patients were randomised into an ORS and CBHG treatment group and a control group for ORS plus placebo. (Average age: 3.2 years). The result of the post-treatment evaluation with respect to the average duration of AD was 25.5 h for the treated group vs. 41.5 h for the control group (p = 0.015). The average number of stools was 4.8 in the treated group and 8.2 in the control group (p = 0.032). We conclude that the use of CBHG plus ORS significantly reduced the duration of AD, the number of stools and the percentage of children with persistent AD after 24 h of treatment compared to the control group. AD remitted almost twice as fast in patients treated with CBHG and ORS compared to those who received ORS plus placebo.
Acceso Abierto
An experiment-informed signal transduction model for the role of the Staphylococcus aureus MecR1 protein in β-lactam resistance
(Springer Nature, 2019-12-20) Belluzo, Bruno Salvador; Abriata, Luciano Andrés; Giannini, Estefanía; Mihovilcevic, Damila; Dal Peraro, Matteo; Llarrull, Leticia Irene
The treatment of hospital- and community-associated infections by methicillin-resistant Staphylococcus aureus (MRSA) is a perpetual challenge. This Gram-positive bacterium is resistant specifically to β-lactam antibiotics, and generally to many other antibacterial agents. Its resistance mechanisms to β-lactam antibiotics are activated only when the bacterium encounters a β-lactam. This activation is regulated by the transmembrane sensor/signal transducer proteins BlaR1 and MecR1. Neither the transmembrane/metalloprotease domain, nor the complete MecR1 and BlaR1 proteins, are isolatable for mechanistic study. Here we propose a model for full-length MecR1 based on homology modeling, residue coevolution data, a new extensive experimental mapping of transmembrane topology, partial structures, molecular simulations, and available NMR data. Our model defines the metalloprotease domain as a hydrophilic transmembrane chamber effectively sealed by the apo-sensor domain. It proposes that the amphipathic helices inserted into the gluzincin domain constitute the route for transmission of the β-lactam-binding event in the extracellular sensor domain, to the intracellular and membrane-embedded zinc-containing active site. From here, we discuss possible routes for subsequent activation of proteolytic action. This study provides the first coherent model of the structure of MecR1, opening routes for future functional investigations on how β-lactam binding culminates in the proteolytic degradation of MecI.
Acceso Abierto
Neurite outgrowth induced by stimulation of angiotensin II AT2 receptors in SH-SY5Y neuroblastoma cells involves c-Src activation
(Elsevier, 2023) Blanco, Helga M.; Perez, Celia N.; Banchio, Claudia; Alvarez, Sergio E.; Ciuffo, Gladys M.
Neuroblastoma, the most common extracranial solid tumor occurring in childhood, originates from the aberrant proliferation of neural crest cells. Accordingly, the mechanism underling neuronal differentiation could provide new strategies for neuroblastoma treatment. It is well known that neurite outgrowth could be induced by Angiotensin II (Ang II) AT2 receptors; however, the signaling mechanism and its possible interaction with NGF (neural growth factor) receptors remain unclear. Here, we show that Ang II and CGP42112A (AT2 receptor agonist) promote neuronal differentiation by inducing neurite outgrowth and βIII-tubulin expression in SH-SY5Y neuroblastoma cells. In addition, we demonstrate that treatment with PD123319 (AT2 receptor antagonist) reverts Ang II or CGP42112A-induced differentiation. By using specific pharmacological inhibitors we established that neurite outgrowth induced by CGP42112A requires the activation of MEK (mitogen-activated protein kinase kinase), SphK (sphingosine ki- nase) and c-Src but not PI3K (phosphatidylinositol 3-kinase). Certainly, CGP42112A stimulated a rapid and transient (30 s, 1 min) phosphorylation of c-Src at residue Y416 (indicative of activation), following by a Src deactivation as indicated by phosphorylation of Y527. Moreover, inhibition of the NGF receptor tyrosine kinase A (TrkA) reduced neurite outgrowth induced by Ang IIand CGP42112A. In summary, we demonstrated that AT2 receptor-stimulated neurite outgrowth in SH-SY5Y cells involves the induction of MEK, SphK and c-Src and suggests a possible transactivation of TrkA. In that regard, AT2 signaling pathway is a key player in neuronal differentiation and might be a potential target for therapeutic treatments.
Acceso Abierto
Involvement of the histone-like nucleoid structuring protein (H-NS) in Acinetobacter baumannii’s natural transformation
(MDPI, 2021-08-26) Le, Casin; Pimentel, Camila; Tuttobene, Marisel Romina; Subils, Tomás; Escalante, Jenny; Nishimura, Brent; Arriaga, Susana; Rodgers, Deja; Bonomo, Robert A.; Sieira, Rodrigo; Tolmasky, Marcelo E.; Ramírez, María Soledad; https://orcid.org/0000-0003-0234-4643; https://orcid.org/0000-0002-4495-563X; https://orcid.org/0000-0002-6298-7811; https://orcid.org/0000-0002-9904-7890
Most Acinetobacter baumannii strains are naturally competent. Although some information is available about factors that enhance or reduce the frequency of the transformation of this bacterium, the regulatory elements and mechanisms are barely understood. In this article, we describe studies on the role of the histone-like nucleoid structuring protein, H-NS, in the regulation of the expression of genes related to natural competency and the ability to uptake foreign DNA. The expression levels of the natural transformation-related genes pilA, pilT, pilQ, comEA, comEC, comF, and drpA significantly increased in a ∆hns derivative of A. baumannii A118. The complementation of the mutant with a recombinant plasmid harboring hns restored the expression levels of six of these genes (pilT remained expressed at high levels) to those of the wild-type strain. The transformation frequency of the A. baumannii A118 ∆hns strain was significantly higher than that of the wild-type. Similar, albeit not identical, there were consequences when hns was deleted from the hypervirulent A. baumannii AB5075 strain. In the AB5075 complemented strain, the reduction in gene expression in a few cases was not so pronounced that it reached wild-type levels, and the expression of comEA was enhanced further. In conclusion, the expression of all seven transformation-related genes was enhanced after deleting hns in A. baumannii A118 and AB5075, and these modifications were accompanied by an increase in the cells’ transformability. The results highlight a role of H-NS in A. baumannii’s natural competence.
Acceso Abierto
Bacterially produced metabolites protect C. elegans neurons from degeneration
(Public Library of Science, 2020-03-24) Urrutia, Arles; Garcia Angulo, Victor Antonio; Fuentes, Andrés; Caneo, Mauricio; Legüe, Marcela; Urquiza Zurich, Sebastian; Delgado, Scarlett E; Ugalde, Juan; Burdisso, Paula; Calixto, Andrea
Caenorhabditis elegans and its cognate bacterial diet comprise a reliable, widespread model to study diet and microbiota effects on host physiology. Nonetheless, how diet influences the rate at which neurons die remains largely unknown. A number of models have been used in C. elegans as surrogates for neurodegeneration. One of these is a C. elegans strain expressing a neurotoxic allele of the mechanosensory abnormality protein 4 (MEC-4d) degenerin/epithelial Na+ (DEG/ENaC) channel, which causes the progressive degeneration of the touch receptor neurons (TRNs). Using this model, our study evaluated the effect of various dietary bacteria on neurodegeneration dynamics. Although degeneration of TRNs was steady and completed at adulthood in the strain routinely used for C. elegans maintenance (Escherichia coli OP50), it was significantly reduced in environmental and other laboratory bacterial strains. Strikingly, neuroprotection reached more than 40% in the E. coli HT115 strain. HT115 protection was long lasting well into old age of animals and was not restricted to the TRNs. Small amounts of HT115 on OP50 bacteria as well as UV-killed HT115 were still sufficient to produce neuroprotection. Early growth of worms in HT115 protected neurons from degeneration during later growth in OP50. HT115 diet promoted the nuclear translocation of DAF-16 (ortholog of the FOXO family of transcription factors), a phenomenon previously reported to underlie neuroprotection caused by down-regulation of the insulin receptor in this system. Moreover, a daf-16 loss-of-function mutation abolishes HT115-driven neuroprotection. Comparative genomics, transcriptomics, and metabolomics approaches pinpointed the neurotransmitter γ-aminobutyric acid (GABA) and lactate as metabolites differentially produced between E. coli HT115 and OP50. HT115 mutant lacking glutamate decarboxylase enzyme genes (gad), which catalyze the conversion of GABA from glutamate, lost the ability to produce GABA and also to stop neurodegeneration. Moreover, in situ GABA supplementation or heterologous expression of glutamate decarboxylase in E. coli OP50 conferred neuroprotective activity to this strain. Specific C. elegans GABA transporters and receptors were required for full HT115-mediated neuroprotection. Additionally, lactate supplementation also increased anterior ventral microtubule (AVM) neuron survival in OP50. Together, these results demonstrate that bacterially produced GABA and other metabolites exert an effect of neuroprotection in the host, highlighting the role of neuroactive compounds of the diet in nervous system homeostasis.
Acceso Abierto
The assembly of bacteria living in natural environments shapes neuronal integrity and behavioral outputs in Caenorhabditis elegans
(American Society for Microbiology, 2023-04-25) Urquiza Zurich, Sebastian; Garcia Angulo, Victor Antonio; Burdisso, Paula; Palominos, M. Fernanda; Fernandez Hubeid, Lucia; Harcha, Paloma A.; Castillo, Juan P.; Calixto, Andrea; https://orcid.org/0000-0002-6168-7286
Bacterivore nematodes are the most abundant animals in the biosphere, largely contributing to global biogeochemistry. Thus, the effects of environmental microbes on the nematodes’ life-history traits are likely to contribute to the general health of the biosphere. Caenorhabditis elegans is an excellent model to study the behavioral and physiological outputs of microbial diets. However, the effects of complex natural bacterial assemblies have only recently been reported, as most studies have been carried out with monoxenic cultures of laboratory-reared bacteria. Here, we quantified the physiological, phenotypic, and behavioral traits of C. elegans feeding on two bacteria that were coisolated with wild nematodes from a soil sample. These bacteria were identified as a putative novel species of Stenotrophomonas named Stenotrophomonas sp. strain Iso1 and a strain of Bacillus pumilus designated Iso2. The distinctive behaviors and developmental patterns observed in animals fed with individual isolates changed when bacteria were mixed. We studied in more depth the degeneration rate of the touch circuit of C. elegans and show that B. pumilus alone is protective, while the mix with Stenotrophomonas sp. is degenerative. The analysis of the metabolite contents of each isolate and their combination identified NAD1 as being potentially neuroprotective. In vivo supplementation shows that NAD1 restores neuroprotection to the mixes and also to individual nonprotective bacteria. Our results highlight the distinctive physiological effects of bacteria resembling native diets in a multicomponent scenario rather than using single isolates on nematodes.
Acceso Abierto
Acinetobacter baumannii response to cefiderocol challenge in human urine
(Springer Nature, 2022-05-24) Nishimura, Brent; Escalante, Jenny; Tuttobene, Marisel Romina; Subils, Tomás; Mezcord, Vyanka; Pimentel, Camila; Georgeos, Nardin; Pasteran, Fernando; Rodríguez, Cecilia; Sieira, Rodrigo; Actis, Luis A.; Tolmasky,, Marcelo E.; Bonomo, Robert A.; Ramírez, María Soledad
Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth. The presence of human urine (HU), which contains low albumin concentrations, did not modify MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in strain AB5075. Expanding the studies to other carbapenem-resistant A. baumannii isolates showed that the presence of HU resulted in unmodified or reduced MIC of CDFC values. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in A. baumannii AMA40 and AB5075 by the presence of HU in the culture medium. All four tested genes code for functions related to recognition and transport of ferric-siderophore complexes. The effect of HU on expression of pbp1, pbp3, blaOXA-51-like, blaADC, and blaNDM-1, genes associated with resistance to β-lactams, as well as genes coding for efflux pumps and porins was variable, showing dependence with the strain analyzed. We conclude that the lack of significant concentrations of albumin and free iron in HU makes this fluid behave differently from others we tested. Unlike other albumin rich fluids, the presence of HU does not impact the antibacterial activity of CFDC when tested against A. baumannii.
Acceso Abierto
2-Mercaptomethyl-thiazolidines use conserved aromatic–S interactions to achieve broad-range inhibition of metallo-β-lactamases
(Royal Society of Chemistry, 2021-01-05) Rossi, María Agustina; Martínez, Verónica; Hinchliffe, Philip; Mojica, María F.; Castillo, Valerie; Moreno, Diego M.; Smith, Ryan; Spellberg, Brad; Drusano, George L.; Banchio, Claudia; Bonomo, Robert A.; Spencer, James; Vila, Alejandro J.; Mahler, Graciela; https://orcid.org/0000-0003-4720-4070; https://orcid.org/0000-0002-3697-5219; https://orcid.org/0000-0001-8611-4743; https://orcid.org/0000-0002-1380-9824; https://orcid.org/0000-0001-5493-8537; https://orcid.org/0000-0002-4602-0571; https://orcid.org/0000-0002-7978-3233; https://orcid.org/0000-0003-0612-0516
Infections caused by multidrug resistant (MDR) bacteria are a major public health threat. Carbapenems are among the most potent antimicrobial agents that are commercially available to treat MDR bacteria. Bacterial production of carbapenem-hydrolysing metallo-β-lactamases (MBLs) challenges their safety and efficacy, with subclass B1 MBLs hydrolysing almost all β-lactam antibiotics. MBL inhibitors would fulfil an urgent clinical need by prolonging the lifetime of these life-saving drugs. Here we report the synthesis and activity of a series of 2-mercaptomethyl-thiazolidines (MMTZs), designed to replicate MBL interactions with reaction intermediates or hydrolysis products. MMTZs are potent competitive inhibitors of B1 MBLs in vitro (e.g., Ki = 0.44 μM vs. NDM-1). Crystal structures of MMTZ complexes reveal similar binding patterns to the most clinically important B1 MBLs (NDM-1, VIM-2 and IMP-1), contrasting with previously studied thiol-based MBL inhibitors, such as bisthiazolidines (BTZs) or captopril stereoisomers, which exhibit lower, more variable potencies and multiple binding modes. MMTZ binding involves thiol coordination to the Zn(II) site and extensive hydrophobic interactions, burying the inhibitor more deeply within the active site than D/L-captopril. Unexpectedly, MMTZ binding features a thioether–π interaction with a conserved active-site aromatic residue, consistent with their equipotent inhibition and similar binding to multiple MBLs. MMTZs penetrate multiple Enterobacterales, inhibit NDM-1 in situ, and restore carbapenem potency against clinical isolates expressing B1 MBLs. Based on their inhibitory profile and lack of eukaryotic cell toxicity, MMTZs represent a promising scaffold for MBL inhibitor development. These results also suggest sulphur–π interactions can be exploited for general ligand design in medicinal chemistry.
Acceso Abierto
Induced Heteroresistance in Carbapenem-Resistant Acinetobacter baumannii (CRAB) via Exposure to Human Pleural Fluid (HPF) and Its Impact on Cefiderocol Susceptibility
(MDPI, 2023-07-21) Mezcord, Vyanka; Escalante, Jenny; Nishimura, Brent; Traglia, German M.; Sharma, Rajnikant; Vallé, Quentin; Tuttobene, Marisel Romina; Subils, Tomás; Marin, Ingrid; Pasteran, Fernando; Actis, Luis A.; Tolmasky, Marcelo E.; Bonomo, Robert A.; Rao, Gauri; Ramírez, María Soledad; https://orcid.org/0000-0003-1896-8450; https://orcid.org/0000-0002-4780-5311; https://orcid.org/0000-0001-5840-5869; https://orcid.org/0000-0001-9644-9088; https://orcid.org/0000-0002-6298-7811; https://orcid.org/0000-0002-9904-7890
Infections caused by Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates, such as hospital-acquired pneumonia (HAP), bacteremia, and skin and soft tissue infections, among others, are particularly challenging to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S. Food and Drug Administration (FDA) in 2019 and prescribed for the treatment of CRAB infections. Despite the initial positive treatment outcomes with this antimicrobial, recent studies reported a higher-than-average all-cause mortality rate in patients treated with cefiderocol compared to the best available therapy. The cause(s) behind these outcomes remains unconfirmed. A plausible hypothesis is heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population that is seemingly isogenic. Recent results have demonstrated that the addition of human fluids to CRAB cultures leads to cefiderocol heteroresistance. Here, we describe the molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations to better understand the nature of the less-than-expected successful outcomes after cefiderocol treatment. Isolation of heteroresistant variants of the CRAB strain AMA40 was carried out in cultures supplemented with cefiderocol and human pleural fluid (HPF). Two AMA40 variants, AMA40 IHC1 and IHC2, were resistant to cefiderocol. To identify mutations and gene expression changes associated with cefiderocol heteroresistance, we subjected these variants to whole genome sequencing and global transcriptional analysis. We then assessed the impact of these mutations on the pharmacodynamic activity of cefiderocol via susceptibility testing, EDTA and boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Heteroresistant variants AMA40 IHC1 and AMA40 IHC2 have 53 chromosomal mutations, of which 40 are common to both strains. None of the mutations occurred in genes associated with high affinity iron-uptake systems or β-lactam resistance. However, transcriptional analyses demonstrated significant modifications in levels of expression of genes associated with iron-uptake systems or β-lactam resistance. The blaNDM-1 and blaADC-2, as well as various iron-uptake system genes, were expressed at higher levels than the parental strain. On the other hand, the carO and ompA genes’ expression was reduced. One of the mutations common to both heteroresistant strains was mapped within ppiA, a gene associated with iron homeostasis in other species. Static time-kill assays demonstrated that supplementing cation-adjusted Mueller–Hinton broth with human serum albumin (HAS), the main protein component of HPF, considerably reduced cefiderocol killing activity for all three strains tested. Notably, collateral resistance to amikacin was observed in both variants. We conclude that exposing CRAB to fluids with high HSA concentrations facilitates the rise of heteroresistance associated with point mutations and transcriptional upregulation of genes coding for β-lactamases and biofilm formation. The findings from this study hold significant implications for understanding the emergence of CRAB resistance mechanisms against cefiderocol treatment. This understanding is vital for the development of treatment guidelines that can effectively address the challenges posed by CRAB infections.
Acceso Abierto
Selective inhibition of the amyloid matrix of Escherichia coli biofilms by a bifunctional microbial metabolite
(Nature Research, 2023-10-19) Cordisco, Estefanía; Zanor, María Inés; Moreno, Diego M.; Serra, Diego Omar; https://orcid.org/0000-0002-6574-1702; https://orcid.org/0000-0002-8903-0673; https://orcid.org/0000-0001-5493-8537; https://orcid.org/0000-0002-3926-384X
The propensity of bacteria to grow collectively in communities known as biofilms and their ability to overcome clinical treatments in this condition has become a major medical problem, emphasizing the need for anti-biofilm strategies. Antagonistic microbial interactions have extensively served as searching platforms for antibiotics, but their potential as sources for anti-biofilm compounds has barely been exploited. By screening for microorganisms that in agar-set pairwise interactions could antagonize Escherichia coli’s ability to form macrocolony biofilms, we found that the soil bacterium Bacillus subtilis strongly inhibits the synthesis of amyloid fibers –known as curli-, which are the primary extracellular matrix (ECM) components of E. coli biofilms. We identified bacillaene, a B. subtilis hybrid non-ribosomal peptide/polyketide metabolite, previously described as a bacteriostatic antibiotic, as the effector molecule. We found that bacillaene combines both antibiotic and anti-curli functions in a concentration-dependent order that potentiates the ecological competitiveness of B. subtilis, highlighting bacillaene as a metabolite naturally optimized for microbial inhibition. Our studies revealed that bacillaene inhibits curli by directly impeding the assembly of the CsgB and CsgA curli subunits into amyloid fibers. Moreover, we found that curli inhibition occurs despite E. coli attempts to reinforce its protective ECM by inducing curli genes via a RpoS-mediated competition sensing response trigged by the threatening presence of B. subtilis. Overall, our findings illustrate the relevance of exploring microbial interactions not only for finding compounds with unknown and unique activities, but for uncovering additional functions of compounds previously categorized as antibiotics.
Acceso Abierto
Factors associated with mortality among hospitalized patients with COVID-19 disease treated with convalescent plasma
(American Society for Microbiology, 2023-11-08) Perichon, Armando M.; Acosta, Andrea; Di Tullio, Liliana; Munuce, María José; Pezzotto, Stella; Bottasso, Oscar; http://orcid.org/0000-0002-8472-7965
The use of convalescent plasma (CP) for hospitalized patients with SARSCoV-2 infection might be a useful option in certain settings. Soon after the outbreak of COVID-19, the National Ministry of Health of Argentina recommended the use of CP transfusion for hospitalized patients with COVID-19 disease. Between 1 June and 3 October 2020, 480 patients, excluding those on invasive mechanical ventilation (IMV), received at least one CP infusion in the province of Santa Fe. We aimed to find factors associated with mortality among this cohort of patients. The median age was 60 years (interquartile range: 49–69 years) and 320 (66.7%) were males. Most of these patients (93.75%) received a single CP infusion, 82.1% and 95.6% before day 4 and day 7 of hospitalization, respectively. Anti-SARS-CoV-2 titers were determined in the CP units administered using Elecsys Anti-SARS-CoV-2 S assay. At 28 days of follow-up, 250 patients were discharged (52.1%), 131 (27.3%) remained hospitalized without and 16 (3.3%) with oxygen requirement, 27 (5.6%) were on IMV, and 56 (11.7%) had died. In the multivariate logistic regression analysis, the factors significantly associated with 28-day mortality were (i) requirement of IMV, (ii) the administration of CP after the third day of hospitalization, (iii) age, and (iv) number of comorbidities. The qualitative and quantitative analyses of antibodies against SARS-CoV-2 in the infused CP were not associated with mortality. Our findings may imply a seemingly favorable effect of CP administration among patients with severe COVID-19 disease when infused sooner after hospitalization.
Acceso Abierto
The iron content of human serum albumin nodulates the susceptibility of Acinetobacter baumannii to Cefiderocol
(MDPI, 2023-02-20) Escalante, Jenny; Nishimura, Brent; Tuttobene, Marisel Romina; Subils, Tomás; Mezcord, Vyanka; Actis, Luis A.; Tolmasky, Marcelo E.; Bonomo, Robert A.; Ramírez, María Soledad
Acceso Abierto
Editorial: Cell polarity: Trafficking and regulatory events that determine cell asymmetry
(Frontiers Media S.A., 2023-01-12) Zucchetti, Andrés E.; Goldenring, James R.; Larocca, María Cecilia
Acceso Abierto
A disordered region retains the full protease inhibitor activity and the capacity to induce CD8+ T cells in vivo of the oral vaccine adjuvant U-Omp19
(Elsevier, 2022-09-06) Darriba, María Laura; Pueblas Castro, Celeste; Coria, Lorena M.; Bruno, Laura; Cerutti, María Laura; Otero, Lisandro H.; Chemes, Lucía B.; Rasia, Rodolfo M.; Klinke, Sebastián; Cassataro, Juliana; Pasquevich, Karina A.
Acceso Abierto
Longitudinal evolution of the Pseudomonas-Derived Cephalosporinase (PDC) structure and activity in a cystic fibrosis patient treated with b-Lactams
(American Society for Microbiology, 2022-09-08) Colque, Claudia A.; Albarracín Orio, Andrea G.; Tomatis, Pablo E.; Dotta, Gina; Moreno, Diego M.; Hedemann, Laura G.; Hickman, Rachel A.; Sommer, Lea M.; Feliziani, Sofía; Moyano, Alejandro José; Bonomo, Robert A.; Johansen, Helle K.; Molin, Soren; Vila, Alejandro J.; Smania, Andrea M.
Acceso Abierto
Human serum albumin (HSA) regulates the expression of histone-like nucleoid structure protein (H-NS) in Acinetobacter baumannii
(Nature Research, 2022-08-27) Escalante, Jenny; Nishimura, Brent; Tuttobene, Marisel Romina; Subils, Tomás; Pimentel, Camila; Georgeos, Nardin; Sieira, Rodrigo; Bonomo, Robert A.; Tolmasky, Marcelo E.; Ramírez, María Soledad
Acceso Abierto
Human Serum Proteins and Susceptibility of Acinetobacter baumannii to Cefiderocol: Role of Iron Transport
(MDPI, 2022-03-03) Le, Casin; Pimentel, Camila; Pasteran, Fernando; Tuttobene, Marisel Romina; Subils, Tomás; Escalante, Jenny; Nishimura, Brent; Arriaga, Susana; Carranza, Aimee; Mezcord, Vyanka; Vila, Alejandro J.; Corso, Alejandra; Actis, Luis A.; Tolmasky, Marcelo E.; Bonomo, Robert A.; Ramírez, María Soledad
Acceso Abierto
Hyponastic leaves 1 is required for proper establishment of auxin gradient in apical hooks
(American Society of Plant Biologists, 2021-10-02) Vacs, Paula; Rasia, Rodolfo M.; González Schain, Nahuel

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