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Marfil-Santana Miguel David,O’Connor-Sánchez Aileen,Ramírez-Prado Jorge Humberto,De los Santos-Briones Cesar,López-Aguiar,Lluvia Korynthia,Rojas-Herrera Rafael,Lago-Lestón Asunción,Prieto-Davó Alejand 한국미생물학회 2016 The journal of microbiology Vol.54 No.11
The need for new antibiotics has sparked a search for the microbes that might potentially produce them. Current sequencing technologies allow us to explore the biotechnological potential of microbial communities in diverse environments without the need for cultivation, benefitting natural product discovery in diverse ways. A relatively recent method to search for the possible production of novel compounds includes studying the diverse genes belonging to polyketide synthase pathways (PKS), as these complex enzymes are an important source of novel therapeutics. In order to explore the biotechnological potential of the microbial community from the largest underground aquifer in the world located in the Yucatan, we used a polyphasic approach in which a simple, non-computationally intensive method was coupled with direct amplification of environmental DNA to assess the diversity and novelty of PKS type I ketosynthase (KS) domains. Our results suggest that the bioinformatic method proposed can indeed be used to assess the novelty of KS enzymes; nevertheless, this in silico study did not identify some of the KS diversity due to primer bias and stringency criteria outlined by the metagenomics pipeline. Therefore, additionally implementing a method involving the direct cloning of KS domains enhanced our results. Compared to other freshwater environments, the aquifer was characterized by considerably less diversity in relation to known ketosynthase domains; however, the metagenome included a family of KS type I domains phylogenetically related, but not identical, to those found in the curamycin pathway, as well as an outstanding number of thiolases. Over all, this first look into the microbial community found in this large Yucatan aquifer and other fresh water free living microbial communities highlights the potential of these previously overlooked environments as a source of novel natural products.
Alicia Alonso-Hernando,Rosa Capita,Miguel Prieto,Carlos Alonso-Calleja 한국미생물학회 2009 The journal of microbiology Vol.47 No.2
Information on the potential for acquired reduced susceptibility of bacteria to poultry decontaminants occurring is lacking. Minimal Inhibitory Concentrations (MICs) were established for assessing the initial susceptibility and the adaptative and cross-adaptative responses of four bacterial strains (Listeria monocytogenes serovar 1/2a, L. monocytogenes serovar 4b, Salmonella enterica serotype Typhimurium, and S. enterica serotype Enteritidis) to four poultry decontaminants (trisodium phosphate, acidified sodium chlorite -ASC-, citric acid, and peroxyacetic acid). The initial susceptibility was observed to differ among species (all decontaminants) and between Salmonella strains (ASC). These inter- and intra-specific variations highlight (1) the need for strict monitoring of decontaminant concentrations to inactivate all target pathogens of concern, and (2) the importance of selecting adequate test strains in decontamination studies. MICs of ASC (0.17±0.02 to 0.21±0.02 mg/ml) were higher than the U.S. authorized concentration when applied as a pre-chiller or chiller solution (0.05 to 0.15 mg/ml). Progressively increasing decontaminant concentrations resulted in reduced susceptibility of strains. The highest increase in MIC was 1.88 to 2.71-fold (ASC). All decontaminants were shown to cause cross-adaptation of strains between both related and unrelated compounds, the highest increase in MIC being 1.82-fold (ASC). Our results suggest that the in-use concentrations of ASC could, in certain conditions, be ineffective against Listeria and Salmonella strains. The adaptative and cross-adaptative responses of strains tested to poultry decontaminants are of minor concern. However, the observations being presented here are based on in vitro studies, and further research into practical applications are needed in order to confirm these findings.
Clavulanic Acid Is a Leading Culprit Beta-Lactam in Immediate Allergic Reactions to Penicillins
Torres-Rojas Isabel,Pérez-Alzate Diana,Somoza Maria Luisa,Pfeifer Ana Prieto-Moreno,Diaz Elisa Haroun,Jimenez-Rodriguez Teodorikez W,Sánchez Javier Fernández,Ruano Francisco J,Blanca Miguel,Blanca-Lóp 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.2
Purpose: Clavulanate, a beta-lactam associated with amoxicillin, is frequently prescribed in patients at all ages. Recent data implicate amoxicillin-clavulanate in up to 80% of beta-lactam allergy cases. We assessed clavulanate’s role in inducing allergic reactions to this combination treatment, with a focus on selective immediate reactions. Methods: Adults (≥ 16 years) reporting a history of immediate reactions to amoxicillin-clavulanate were evaluated through a beta-lactam allergological workup, using modified European Academy of Allergy and Clinical Immunology guidelines. Patients first underwent skin testing, and if negative, drug provocation tests. Expected outcomes were: Group A, subjects with immediate reaction to classical penicillin group determinants (penicilloyl polylysine, minor determinants mixture, and/or penicillin G); Group B, subjects with selective immediate reaction to amoxicillin; Group C, subjects with selective immediate reaction to clavulanate and Group D, those immediate reactions with co-sensitization to clavulanate plus penicillin group determinants or amoxicillin. Results: Of 1,170 included patients, 104 had immediate reactions: 36.5% to penicillin group determinants (Group A), 26.9% to amoxicillin (Group B), 32.7% to clavulanate (Group C), and 3.8% to clavulanate plus penicillin determinants or amoxicillin (Group D). Diagnosis was made by skin testing in 79%, 75% and 47% of the patients, respectively, in the first 3 groups (P < 0.001). Drug provocation tests were necessary to establish most other diagnoses. Anaphylaxis predominated over urticaria/angioedema in all groups. Conclusions: Selective immediate reactions to clavulanate accounted for over a third of cases with confirmed reactions after amoxicillin-clavulanate intake, with more than half experiencing anaphylaxis. Within this group, skin test sensitivity was below 50%. People taking amoxicillin-clavulanate may also be co-sensitized to both drugs.
A rare case of choledochal cyst with pancreas divisum
Adrian Ransom-Rodriguez,Ruben Blachman-Braun,Emilio Sanchez-Garcia Ramos,Jesus Varela-Prieto,Erick Rosas-Lezama,Miguel Angel Mercado 한국간담췌외과학회 2017 Annals of hepato-biliary-pancreatic surgery Vol.21 No.1
Choledochal cysts are rare congenital malformations of the bile duct characterized by dilatations of the intrahepatic and/or extrahepatic portion of the biliary tree, they are associated to an anomalous arrangement of the pancreaticobiliary duct. Pancreas divisum results from a fusion failure of the pancreatic buds. The coexistence of pancreas divisum and choledochal cyst in adults has been reported in less than 10 well documented cases. This article presents a case of a 42-year-old Peruvian man with intermittent episodes of abdominal pain, initially diagnosed with choledocholithiasis, who underwent open cholecystectomy. During surgery, a diagnosis of choledochal cyst and pancreas divisum was made, and therefore a hepaticoduodenostomy was performed. The patient was referred to our hospital due to persistence of abdominal pain. After admission, a papillectomy was achieved without further complications. A cyst resection and dismantling of hepaticoduodenostomy with Roux-en-Y was performed 8 years later. During the subsequent 18-month follow-up, the patient remains asymptomatic.
Etiopathogenic role of ERK5 signaling in sarcoma: prognostic and therapeutic implications
Sánchez-Fdez Adrián,Matilla-Almazán Sofía,Del Carmen Sofía,Abad Mar,Arconada-Luque Elena,Jiménez-Suárez Jaime,Chinchilla-Tábora Luis Miguel,Ruíz-Hidalgo Mª José,Sánchez-Prieto Ricardo,Pandiella Atanas 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Sarcomas constitute a heterogeneous group of rare and difficult-to-treat tumors that can affect people of all ages, representing one of the most common forms of cancer in childhood and adolescence. Little is known about the molecular entities involved in sarcomagenesis. Therefore, the identification of processes that lead to the development of the disease may uncover novel therapeutic opportunities. Here, we show that the MEK5/ERK5 signaling pathway plays a critical role in the pathogenesis of sarcomas. By developing a mouse model engineered to express a constitutively active form of MEK5, we demonstrate that the exclusive activation of the MEK5/ERK5 pathway can promote sarcomagenesis. Histopathological analyses identified these tumors as undifferentiated pleomorphic sarcomas. Bioinformatic studies revealed that sarcomas are the tumors in which ERK5 is most frequently amplified and overexpressed. Moreover, analysis of the impact of ERK5 protein expression on overall survival in patients diagnosed with different sarcoma types in our local hospital showed a 5-fold decrease in median survival in patients with elevated ERK5 expression compared with those with low expression. Pharmacological and genetic studies revealed that targeting the MEK5/ERK5 pathway drastically affects the proliferation of human sarcoma cells and tumor growth. Interestingly, sarcoma cells with knockout of ERK5 or MEK5 were unable to form tumors when engrafted into mice. Taken together, our results reveal a role of the MEK5/ERK5 pathway in sarcomagenesis and open a new scenario to be considered in the treatment of patients with sarcoma in which the ERK5 pathway is pathophysiologically involved.