Pulmonary Pathogens Adapt to Immune Signaling Metabolites in the Airway.

A limited number of pulmonary pathogens are able to evade normal mucosal defenses to establish acute infection and then adapt to cause chronic pneumonias. Pathogens, such as Pseudomonas aeruginosa or Staphylococcus aureus, are typically associated with infection in patients with underlying pulmonary disease or damage, such as cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). To establish infection, bacteria express a well-defined set of so-called virulence factors that facilitate colonization and activate an immune response, gene products that have been identified in murine models. Less well-understood are the adaptive changes that occur over time in vivo, enabling the organisms to evade innate and adaptive immune clearance mechanisms. These colonizers proliferate, generating a population sufficient to provide selection for mutants, such as small colony variants and mucoid variants, that are optimized for long term infection. Such host-adapted strains have evolved in response to selective pressure such as antibiotics and the recruitment of phagocytes at sites of infection and their release of signaling metabolites (e.g., succinate). These metabolites can potentially function as substrates for bacterial growth and but also generate oxidant stress. Whole genome sequencing and quantified expression of selected genes have helped to explain how P. aeruginosa and S. aureus adapt to the presence of these metabolites over the course of in vivo infection. The serial isolation of clonally related strains from patients with cystic fibrosis has provided the opportunity to identify bacterial metabolic pathways that are altered under this immune pressure, such as the anti-oxidant glyoxylate and pentose phosphate pathways, routes contributing to the generation of biofilms. These metabolic pathways and biofilm itself enable the organisms to dissipate oxidant stress, while providing protection from phagocytosis. Stimulation of host immune signaling metabolites by these pathogens drives bacterial adaptation and promotes their persistence in the airways. The inherent metabolic flexibility of P. aeruginosa and S. aureus is a major factor in their success as pulmonary pathogens.

Cellular Membrane Composition Requirement by Antimicrobial and Anticancer Peptide GA-K4.

Naturally occurring antimicrobial peptides important for innate immunity are widely studied for their antimicrobial and anticancer activity. The primary target of these AMPs is believed to be the bacterial cytoplasmic membrane. However, the interaction between cytoplasmic membrane and the antimicrobial peptides remains poorly understood. Therefore to focus on the target membrane composition that is required by AMPs to interact with membranes, we have examined the interaction of the antimicrobial and anticancer active 11-residue GA-K4 (FLKWLFKWAKK) peptide with model and intact cell membranes. Effect on the structural conformational properties of GA-K4 peptide was investigated by means of far-UV CD and fluorescence spectroscopic methods. The different conformation of GA-K4 peptide in large unilamellar vesicles (LUV) bilayer and micelle environment suggest that the curvature has an influence on the secondary structure acquired by the peptide. Furthermore, the leakage experiment result confirmed that GA-K4 induced the leakage of cytoplasmic membrane in Staphylococcus аureus bacterial cells. Fluorescence data revealed the interfacial location of GA-K4 peptide in the model membranes. The blue-shift in emission wavelength by tryptophan residues in fluorescence data indicated the penetration of GA-K4 peptide in micelles and phospholipid bilayers. These results showed that the GA-K4 peptide is a membrane-active peptide and its activity depends on membrane curvature and lipid composition. Although further studies are required to confirm the mechanism of action, the data suggest mechanism of toroidal pore formation for the interaction of GA-K4 peptide with membranes. Our studies will be helpful in better understanding of the membrane requirment of peptides to express their therapeutic effects.

Absceso renal estafilocócico trasforunculosis cutánea / Staphylococcus renal abscess after cutaneous furunculosis

Los abscesos renales son patologías infrecuentes, pero de alta morbi-mortalidad si no son diagnosticados temprano y tratados precozmente. Su vaga e inespecífica sintomatología: dolor abdominal o lumbar, fiebre o mal estado general hacen que su diagnostico sea a veces tardío. La ecografía y/o la TAC dan el diagnóstico en el 100 por ciento de los casos lo que hace posible su tratamiento temprano. El objetivo de este artículo es poner de relieve que el absceso renal es una causa de urgencia urológica a tener presente en pacientes fundamentalmente del sexo femenino, con síntomas de dolor abdominal o fiebre sin clara focalidad urológica.MATERIAL Y MÉTODOS: Se presenta el caso de una adolescente de 16 años con antecedente reciente de forunculosis cutánea supurada en rodilla derecha, que acudió a urgencias por dolor en flanco derecho y fosa iliaca derecha de 10 días de evolución sin fiebre ni síntomas miccionales. Se nos consultó para su valoración, siendo la ecografía el método diagnóstico que se utilizó para la localización de un absceso renal derecho subcapsular de 44 mm en polo superior, y posteriormente para su drenaje percutáneo al no responder porcompleto al tratamiento antibiótico i.v. El cultivo del material purulento del drenaje percutáneo aisló un Staphyloccocus aureus no meticilin resistente. El tratamiento antibiótico i.v asociado a drenaje percutáneo seguido de cloxacilina oral a su alta, curó a la paciente. A raíz de este caso se revisan las series y revisiones sobre abscesos renales de los últimos 10 años, con un total de 179 pacientes, y las publicaciones sobre abscesos renales por Staphyloccocus aureus con tan sólo 13 casos. CONCLUSIONES: Los abscesos renales han de tenerse en cuenta entre las urgencias urológicas. Su diagnóstico y tratamiento percutáneo es mayormente radiológico, reservándose la cirugía abierta o la nefrectomía para abscesos > de 5 cm o pacientes sépticos...

Renal abscesses are infrequent pathologies, but with a high morbidity-mortality if they are not diagnosed and treated early. Its vague and unspecific symptomatology: abdominal or lumbar pain, fever or poor general state, make its diagnosis late sometimes. The ultrasound and/or TAC provide a 100 percent diagnosis of the cases where its early treatment is possible. The objective of this article is to give importance to the fact that renal abscess is a cause of an urological emergency to keep in mind in patients, particularly females with symptoms of abdominal pain or fever without a clear urological focus. MATERIAL AND METHODS: The case of a 16-year-old adolescent is presented with a recent history of festered cutaneous furunculosis on the right knee. She went to the emergency room due to pain on the right side and right illiac fosa with 10 days evolution without fever or urinary symptoms. She came to us for its evaluation, an ultrasound was used for diagnosis to locate a right subcapsular renal abscess of 44 mm on the superior pole, and later for its percutaneous drainage when it did not completely responded to I.V. antibiotic treatment. The culture of the purulent material of the percutaneous drainage isolated a resistant non-methicillin Staphyloccocus aureus. The I.V. antibiotic treatment associated to percutaneous drainage followed by oral cloxacillin upon release cured the patient. CONCLUSIONS: Renal abscesses have to be taken into account among the urological emergencies. Their diagnosis and percutaneous treatment is mainly radiological, leaving open surgery or nephrectomy for abscesses > 5cm or with septic patients...

Infecciones por Staphylococcus aureus meticilino resistente en niños en Bucaramanga Colombia / Methicillin-resistant Staphylococcus aureus infections in children in Bucaramanga Colombia

Introducción: La emergencia de infecciones, en niños, por Staphylococcus aureus meticilino resistente adquirido en comunidad (SAMR-AC) en niños constituye un problema de salud pública en varios países del mundo, sin embargo, en nuestro país hay pocos reportes sobre las características clínicas, factores de riesgo y características moleculares. Materiales y métodos: Estudio descriptivo que comparó el comportamiento clínico y epidemiológico de las infecciones por S. aureus meticilino resistente y S. aureus meticilino sensible. Se detectaron los genes mecA, lukS-PV y lukF-PV por amplificación y se determinó la resistencia a antimicrobianos. Resultados: De las 39 infecciones por S. aureus entre enero de 2008 y junio de 2009, el 60% fueron por S. aureus meticilino resistente, con mayor proporción de lactantes y uso previo de antibióticos en el grupo meticilino resistente. Predominó la localización Osteoarticular (54%) seguida de piel y tejidos blandos (41%). En los meticilino resistentes el gen mecA y lukS-PV y lukF-PV se detectaron en el 93% y 86% respectivamente. En el grupo meticilino resistentes y leucocidina de Panton Valentine positiva fueron más frecuentes los abscesos subcutáneos, una mayor respuesta inflamatoria y susceptibilidad a la mayoría de los antibióticos. Conclusión: Reportamos la presencia de infecciones por SAMR – AC (LPV +, con susceptibilidad a la mayoría de los antibióticos) en nuestro medio, con abscesos como foco clínico predominante y una mayor respuesta inflamatoria.

Introduction: The emergence of the infection by community-acquired methicillin-resistant S. aureus, in children, is a public health problem in many countries of the world, however, in Colombia, local dates about the clinical features, risk factors and molecular characteristic are scarce. Materials and methods: This descriptive study compared the clinical and epidemiological behavior of infections by methicillin-resistant S. aureus and methicillin suceptible S. aureus. The gen mecA and lukS-PV y lukF-PV were detected by amplification and antibiotic sensitivity was determinated. Results:From January 2008 to June de 2009, 39 infections caused by S. aureus were diagnosed, 60% by methicillin-resistant S. aureus. In the group methicillin-resistant, there were more proportion of infants and previous use of antibiotics. The most frequents location of the infection were: Osteoarticular (54%) and Skin and soft tissue (41%). The gen mecA and lukSPV y lukF-PV were detected in 93% and 86% of the methicillin-resistant S. aureus. Soft tissue abscess, an inflammatory response enhanced and sensitivity to the most of the antibiotics were most frequent in the group methicillin-resistant and Panton-Valentine leuokocidin (PVL) positive. Conclusions: We report the presence of infections by MRSA – AC, PVL + and sensitivity to the most of antibiotics, in our media. The most frequent features are the presence of soft tissue abscesses and an inflammatory response enhanced.