Miguel Viñas

Interactions between pairs of bacteriocins from lactic bacteria.

Activity of pairs of crude extracts of lactic acid bacteria (LAB) containing different bacteriocins (nisin, pediocin AcH, lacticin 481, lactacin F, and lactacin B) was measured against 10 different indicator strains. Experiments were carried out both in liquid and on solid media. Both synergisms and antagonisms were observed. Lacticin 481 produced mainly antagonistic effects whereas pediocin AcH produced mainly synergistic effects. The use of more than one LAB bacteriocin as a combination biopreservative might be envisaged.

New Insights on the Antitumoral Properties of Prodiginines

Apoptosis is involved in the action of several (and perhaps all) cancer-chemotherapeutic agents. Prodiginines are a family of natural red pigmented secondary metabolites, produced by different bacteria and most of them are characterized by a common pyrrolylpyrromethene skeleton. The biosynthesis of prodigiosin and derivatives has been extensively studied in Serratia marcescens. S. marcescens is a Gramnegative bacterium belonging to Enterobacteriaceae. Prodiginines show numerous biological activities pointing out immunosuppressive and anticancer properties. Some prodiginines displayed apoptotic effects in vitro and antitumor activity in vivo. Their cytotoxic effect is attributed to the presence of the C- 6 methoxy substituent. The A-pyrrole ring plays a key role in both the copper nuclease activity and the cytotoxicity of prodiginines. Here we review the main characteristics of prodigiosin and their derivatives as well as the most prominent pharmacological activity of prodiginines and related compounds, including novel synthetic PG-derivatives with lower toxicity like GX15-070 (Obatoclax). The molecular targets of prodiginines are discussed and the mechanism of action for these molecules is a current topic in biomedicine with a real therapeutica potential in the clinic.

Class 1 integrons in environmental and clinical isolates of Pseudomonas aeruginosa

The aims of this study were to ascertain the presence and spread of class 1 integrons amongst environmental and clinical isolates of Pseudomonas aeruginosa and to characterise their variable regions. A total of 76 isolates (56 clinical and 20 environmental) were studied. The presence of plasmids was explored, and polymerase chain reaction (PCR) was used for integron detection. All amplicons were sequenced. PCR detected class 1 integrons in 26 of the 56 clinical isolates; environmental isolates were integron-free. No plasmids were found, thus all the integrons found are possibly on the chromosome. Most isolates presented one amplicon, except PA110514 and PA116136, which showed two PCR products each. Variable regions revealed that 18 strains carried only one gene involved in aminoglycoside resistance, whereas in 3 strains gene cassettes were not found. The most prevalent cassettes amongst isolates were those encoding aminoglycoside adenyltransferase B (aadB). Several of the strains had acquired the same or a highly similar cassette array as those detected in geographically distant P. aeruginosa. This finding suggests that contact with bacterial reservoirs contributes to the evolution of this pathogen towards multiresistance. Empty structures found may represent a reservoir increasing the capacity to adapt to the environment. However, these integrons are not retained when the selective pressure disappears. It is hypothesised that integrons containing gene cassettes are crucial vehicles for the rapid horizontal transfer of resistance. If this is so, reduced use of antibiotics may lead to a significant decrease in the carriage of integrons amongst P. aeruginosa strains.

Risk factors for denture-related oral mucosal lesions in a geriatric population

STATEMENT OF PROBLEM Denture-related mucosal lesions have been broadly studied. However, no consensus has been reached regarding the risk factors associated with these lesions, and few studies have used multivariable analysis to determine the relative significance of different risks. PURPOSE The purpose of this study was to determine the relationship between systemic, local, and denture factors on the risk of denture-related oral mucosal lesions in an elderly population by using multivariable analysis. MATERIAL AND METHODS Eighty-four elderly denture wearers recruited from geriatric residences and day care centers participated in this cross-sectional study. All data were obtained by means of a questionnaire-interview, a physical examination, and complementary tests. Bivariate relationship and multiple logistic regression analyses were performed (α=.05). RESULTS Angular cheilitis (34%), traumatic ulcers (15%), and denture stomatitis (14%) were the 3 most common lesions, and the prevalence of at least 1 denture-related mucosal lesion was 54%. The presence of denture stomatitis was related to low saliva pH, never having smoked, and regular sugar consumption. Angular cheilitis was associated with age, complete edentulism, the presence of oral Candida, a lack of denture stability, and a reduced occlusal vertical dimension. The presence of traumatic ulcers was related to a resorbed residual alveolar ridge. The presence of at least 1 lesion was associated with poor masticatory efficiency, being resident in a care facility, oral Candida, and a lack of denture stability. CONCLUSIONS Several systemic, local, and denture-related characteristics are independent risk factors for denture-related mucosal lesions in an elderly population.

Neisseria lactamica and Neisseria polysaccharea as possible sources of meningococcal beta-lactam resistance by genetic transformation.

We studied the susceptibilities of relatively penicillin G-resistant and -susceptible strains of Neisseria meningitidis, as well as Neisseria lactamica and Neisseria polysaccharea, to penicillin, ampicillin, and several cephalosporins. The MICs of penicillin, ampicillin, cephalothin, and cefuroxime for moderately resistant meningococci have increased two- to sixfold in relation to MICs for susceptible strains. For these strains of meningococci, N. lactamica, and N. polysaccharea, penicillin, ampicillin, cephalothin, and cefuroxime MICs for 50 and 90% of strains were similar. By genetic transformation of a penicillin-susceptible strain of N. meningitidis to low-level penicillin resistance with DNA from penicillin-resistant strains of N. meningitidis, N. lactamica, N. polysaccharea, and N. gonorrhoeae, isogenic strains with the same pattern of resistance to beta-lactams were obtained, suggesting that these commensal Neisseria spp. could be the source of meningococcal resistance genes.

An overview of antimicrobial peptides and the latest advances in their development

ABSTRACT Introduction: The recent dramatic increase in the incidence of antimicrobial resistance has been recognized by organizations such as the United Nations and World Health Organization as well as the governments of the USA and several European countries. A relatively new weapon in the fight against severe infections caused by multi-drug resistant bacteria is antimicrobial peptides (AMPs). These include colistin, currently regarded as the last line of antimicrobial therapy against multi-drug resistant microorganisms. Areas covered: Here, the authors provide an overview of the current research on AMPs. The focus is AMPs currently being developed for the treatment of recalcitrant bacterial infections, the synergies of AMPs and antibiotics, and the activity of AMPs against biofilm. This review also includes a brief introduction into the use of AMPs in infections caused by Mycobacterium, fungi, and parasites. Expert opinion: In research into new antimicrobials, AMPs are gaining increasing attention. While many are natural and are produced by a wide variety of organisms, others are being newly designed and chemically synthesized in the laboratory to achieve novel antimicrobial agents. The same strategy to fight infections in nature is thus being effectively exploited to safeguard human and animal health.

A generalized transducing bacteriophage for Serratia marcescens

Using Serratia marcescens 2170 harbouring plasmid pTroy11 (encoding for LamB), and lambda (lambda:: Tn5) we constructed a collection of 25 auxotrophic mutations induced by Tn5 insertions. These mutants permitted the use an easy screening method for generalized transducing bacteriophages. Out of twelve bacteriophages isolated from natural sources only one (phage 3M) was able to transduce all Tn5 insertions tested. The preliminary characterization of bacteriophage 3M indicates that it belongs to the Myoviridae family.

Evidence of an Efflux Pump in Serratia marcescens

Spontaneous mutants resistant to fluoroquinolones were obtained by exposing Serratia marcescens NIMA (wild-type strain) to increasing concentrations of ciprofloxacin both in liquid and on solid media. Frequencies of mutation ranged from 10(-7) to 10(-9). Active expulsion of antibiotic was explored as a possible mechanism of resistance in mutants as well as changes in topoisomerase target genes. The role of extrusion mechanisms in determining the emergence of multidrug-resistant bacteria was also examined. Mutants resistant to high concentrations of fluoroquinolones had a single mutation in their gyrA QRDR sequences, whereas the moderate resistance in the rest of mutants was due to extrusion of the drug.

Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis

Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudomonas aeruginosa is the main pathogen in the pulmonary infection of these patients. In this work, we developed sodium colistimethate loaded lipid nanoparticles, namely, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), as a strategy to enhance the antimicrobial therapy against P. aeruginosa in cystic fibrosis patients. The nanoparticles obtained displayed a 200-400 nm size, high drug entrapment (79-94%) and a sustained drug release profile. Moreover, both SLN and NLC presented antimicrobial activity against clinically isolated P. aeruginosa. The integrity of the nanoparticles was not affected by nebulization through a mesh vibrating nebulizer. Moreover, lipid nanoparticles appeared to be less toxic than free sodium colistimethate in cell culture. Finally, an in vivo distribution experiment showed that nanoparticles spread homogenously through the lung and there was no migration of lipid nanoparticles to other organs, such as liver, spleen or kidneys.

Mechanisms other than penicillin-binding protein-2 alterations may contribute to moderate penicillin resistance in Neisseria meningitidis

Penicillin resistance in Neisseria spp is thought to be generated by the interspecies transfer of genetic material from naturally penicillin-resistant, commensal species. We examined a series of successive transformants with increasing levels of penicillin resistance, obtained by co-cultivation of Neisseria meningitidis derivatives with Neisseria polysaccharea. Our results suggest that, in addition to the well-known decrease in penicillin affinity of penicillin-binding protein-2 (PBP-2), decreased expression of the class 3 porin as well as decreased affinity of PBP-1 may contribute to higher level resistance of N. meningitidis to penicillin G and other beta-lactam compounds.