Down Regulation of Catsper1 Expression by Calmodulin Inhibitor (Calmidazolium): Possible Implications for Fertility.

The CatSper channel localizes exclusively in the flagella of sperm cells. The Catsper1 protein, together with three pore units, is essential for the CatSper Channel formation, which produces flagellum hyperactivation and confers sperm fertility. Catsper1 expression is dependent on Sox transcription factors, which can recognize in vitro at least three Sox binding sites on the promoter. Sox transcription factors have calmodulin-binding domains for nuclear importation. Calmodulin (CaM) is affected by the specific inhibitor calmidazolium (CMZ), which prevents the nuclear transport of Sox factors. In this work, we assess the regulation of the Catsper1 promoter in vivo by Sox factors in the murine testis and evaluate the effects of the inhibitor calmidazolium on the expression of the Casper genes, and the motility and fertility of the sperm. Catsper1 promoter has significant transcriptional activity in vivo; on the contrary, three Sox site mutants in the Catsper1 promoter reduced transcriptional activity in the testis. CaM inhibition affects Sox factor nuclear transport and has notable implications in the expression and production of Catsper1, as well as in the motility and fertility capability of sperm. The molecular mechanism described here might conform to the basis of a male contraceptive strategy acting at the transcriptional level by affecting the production of the CatSper channel, a fundamental piece of male fertility.

Percepción de riesgos en la salud de la comunidad indígena Mixteca El Calvario, al sur de México / Perception of health risks in the Mixteca El Calvario indigenous community in southern Mexico

La situación de salud y percepción de riesgos de las comunidades indígenas se mide por el grado sociodemográfico y estudio etnográfico. Nuestra población en estudio “El Calvario” es la única comunidad indígena Mixteca de Chilpancingo, Guerrero, conformada por 21 familias que se dedican a la agricultura, producción de maguey y mezcal, y elaboración de algunas artesanías de palma. El objetivo fue estudiar las condiciones de Calidad de Vida y percepción de riesgos en dos grupos vulnerables adultos y niños. En el caso de los adultos, se hizo por encuestas y en el caso de los niños se usó el dibujo. En los habitantes se perciben en riesgos de salud y de perder su identidad indígena, debido a que solo hablan su lengua materna los adultos, no saben leer y ni escribir. Así mismo, es inminente el riesgo de sufrir daños materiales debido a que las viviendas no son adecuadas. La migración de jóvenes, la perdida de cultura, el padecer enfermedades metabólicas debido a la dieta alta en refrescos. Así mismo, los niños expresaron las deficiencias educativas. Finalmente, la población en general se encuentra olvidada por los organismos de gobierno actuales, en riesgo sanitario, y de perdida de cultura ya que los jóvenes migrarán a otros lugares a buscar nuevas oportunidades. Es un fuerte llamado de atención a la sociedad ya que, de no actuar en consecuencia con dicha problemática, se perdería la única comunidad Mixteca en Chilpancingo, Guerrero.(AU)

The health situation and risk perception of indigenous communities is measured by sociodemographic grade and ethnographic study. Our study population "El Calvario" is the only Mixtec indigenous community in Chilpancingo, Guerrero, made up of 21 families that are dedicated to agriculture, production of maguey and mezcal, and making some palm handicrafts. The objective was to study the conditions of Quality of Life and risk perception in two vulnerable groups, adults and children. In the case of adults, it was done through surveys and in the case of children, drawing was used. The inhabitants are perceived as being at risk of health and of losing their indigenous identity, because only adults speak their mother tongue, they do not know how to read and write. Likewise, the risk of suffering material damage is imminent due to the inadequate housing. The migration of young people, the loss of culture, suffering from metabolic diseases due to a diet high in soft drinks. Likewise, the children expressed educational deficiencies. Finally, the general population is forgotten by current government agencies, at risk of health, and loss of culture as young people will migrate to other places to seek new opportunities. It is a strong call for attention to society since, if it does not act accordingly, the only Mixtec community in Chilpancingo, Guerrero, would be lost.(AU)

Portadores asintomáticos de Staphylococcus aureus meticilino resistentes (MRSA) en pescadores y horticultores de Guerrero, México / Asymptomatic carriers of resistant methicillin Staphylococcus aureus (MRSA) in fishermen and horticulturists in Guerrero, Mexico

Staphylococcus aureus resistente a la meticilina (SARM) ha sido considerado clásicamente un patógeno oportunista, causante de diversas infecciones en humanos y animales, es resistente a múltiples antibióticos característica que dificulta su control y tratamiento, se encuentra en las fosas nasales de personas sanas y se denomina estado de portador que produce motivos de alarma, desde su aparición en la década de los 70s, lo cual se ha diseminado de tal forma que hoy es el patógeno más importante del mundo considerado un problema de salud pública. OBJETIVO: Determinar la presencia de Staphylococcus aureus meticilino resistentes (SAMR) en portadores asintomáticos, pescadores y horticultores de Guerrero, México. METODOLOGÍA: Se detectaron portadores asintomáticos en pescadores y horticultores en el estado de Guerrero. Se tomaron 107 muestras nasales, se cultivaron e identificaron cepas de S. aureus con pruebas bioquímicas convencionales, las cepas MRSA se evaluaron mediante el método de difusión de disco, por la técnica de Kirby-Bauer, siguiendo las normas internacionales del CLSI. RESULTADOS: Se detectaron por la resistencia a la oxacilina y ser cefoxitina positivos, de los resultados obtenidos de 57 pescadores y 50 horticultores, solo se logró detectar cuatro cepas MRSA en los pescadores, la detección de estas cepas en el ambiente podría ser importante. CONCLUSIÓN: La presencia de S. aureus resulta de trascendencia epidemiológica dado que se puede transmitir de personas-personas, manipuladores de alimentos que portan ya que S. aureus productores de enterotoxinas causan intoxicaciones alimentarias, es por ello que este es el primer reporte del estado de portador de MRSA en pescadores y horticultores en el estado de Guerrero. Por lo mismo se requiere poner atención, ya que de lo contrario los resultados en salud pública podrían ser negativos

Methicillin-resistant Staphylococcus aureus (MRSA) has been classically considered an opportunistic pathogen, causing various infections in humans and animals, it is resistant to multiple specific antibiotics that hinder its control and treatment, it is found in the nasal passages of healthy people and it has been called a carrier state that produces reasons for alarm, since its appearance in the 1970s, which has spread in such a way that today it is the most important pathogen in the world considered a public health problem. AIM: METODOLOGY: Asymptomatic carriers were detected in fishermen and horticulturists in the state of Guerrero. 107 nasal samples were taken, S. aureus strains were cultivated and identified with specific biochemical tests, MRSA strains were evaluated by the disk diffusion method, by the Kirby-Bauer technique, following the international standards of CLSI. RESULTS: Were detected by resistance to oxacillin and being cefoxitin positive, of the results detected from 57 fishermen and 50 horticulturists, only four MRSA They were detected due to resistance to oxacillin and being cefoxitin positive. From the results obtained from 57 fishermen and 50 horticulturists, only four MRSA strains were detected in fishermen; detection of these strains in the environment could be important. CONCLUSION: The presence of S. aureus is of epidemiological significance since it can be transmitted from people to people, food handlers that carry, since S. aureus, producers of enterotoxins, cause food poisoning, which is why this is the first report on carrier status of MRSA in fishermen and horticulturists in the state of Guerrero. Therefore, it is necessary to pay attention, since otherwise the results in public health could be negative

Filogeografía de glmM en cepas de Helicobacter pylori aisladas de pacientes con patologías gástricas al sur de México / Phylogeography of glmM in Helicobacter pylori strains isolated from patients with gastric pathologies in southern Mexico

INTRODUCCIÓN: Helicobacter pylori posee un genoma de aproximadamente 1600 genes, el gen glmM está altamente conservado y se ha utilizado para identificar H. pylori por su sensibilidad y especificidad en biopsias gástricas. La diversidad genética de H. pylori es alta entre cepas del mismo origen geográfico y es aún más a escala global. En México, son pocos los estudios que destacan la importancia de la variabilidad genética de esta bacteria, la cual es estudiada mediante técnicas moleculares. OBJETIVO: Analizar la variabilidad genética del gen glmM en cepas de H pylori de pacientes con patologías gástricas. METODOLOGÍA: Se analizaron solo 90 secuencias del gen glmM (10 de grupo de estudio y 80 depositadas en el GenBank), posteriormente realizamos redes de haplotipos, donde se puede observar las diferencias en pasos mutacionales de las secuencias a nivel estatal y con otros grupos geográficos con el fin de hacer una reconstrucción de filogenia basada en las relaciones ancestro-descendiente. RESULTADOS: Las cepas analizadas provenían el 30% hombres y 70% mujeres, con una edad promedio de 42 años, con diagnóstico de gastritis, las secuencias de glmM mostraron variabilidad genética. De las secuencias analizadas, se propone confirmar la presencia de ocho haplotipos que se agrupan separados. CONCLUSIONES: Se sugiere hacer estudios detallados a nivel molecular de los haplotipos del gen glmM en cepas de H. pylori para conocer su distribución geográfica con la finalidad de conocer las cepas circulantes a nivel mundial y con esto evitar los resultados negativos

INTRODUCTION: Helicobacter pylori has a genome of approximately 1600 genes, the glmM gene is highly conserved and has been identified to identify H. pylori due to its sensitivity and specificity in gastric biopsies. The genetic diversity of H. pylori is high among strains of the same geographical origin and is even more of a global scale. In Mexico, studies that study the importance of the genetic variability of this bacterium, which is studied by molecular techniques. AIM: To analyze the genetic variability of the glmM genus in H pylori strains of patients with gastric pathologies. METHODOLOGY: Only 90 sequences of the glmM genus were analyzed (10 of study group and 80 deposit in GenBank), to carry out haplotype networks, where the differences in the steps of the relationships at the state level and with other geographical groups can be observed in order to do a reconstruction of phylogeny based on ancestor-descendant relationships. RESULTS: The strains analyzed showed 30% of men and 70% of women, with an average age of 42 years, diagnosed with gastritis, the glmM sequences. From the sequences analyzed, it is proposed to confirm the presence of eight haplotypes that are grouped separately. CONCLUSIONS: We suggest university studies at the molecular level of the glmM haplotypes in strains of H. pylori to know their geographical distribution in order to know the circulating strains worldwide and with this avoid negative results

Significados del conflicto armado en adolescentes, jóvenes y adultos mayores de Bucaramanga, Colombia / Meanings of armed conflict in adolescents, youth and older adults in Bucaramanga, Colombia

Resumen Los significados sobre el conflicto armado se construyen a partir de la cercanía y las experiencias que las poblaciones tienen frente a dicho fenómeno. El presente estudio tuvo como objetivo explorar los significados que tenían del conflicto armado 22 adolescentes y jóvenes y 20 adultos mayores de Bucaramanga. Con un diseño cualitativo, enfoque fenomenológico y muestreo a conveniencia, se utilizó una entrevista a profundidad y se construyó un grupo focal. Los resultados evidenciaron categorías sobre percepción, conocimiento, valoración e ideas de solución. Se encontró que los adultos mayores refieren más hechos relacionados al conflicto en comparación con los adolescentes y los jóvenes. En relación con la valoración del conflicto, ambos grupos lo perciben como algo atroz e injusto. También señalan que estos delitos los generaban grupos como la guerrilla, las FARC, el ELN, o el M-19. La corrupción también se destacó en el discurso de los participantes. Respecto a las soluciones al conflicto armado, resaltó el diálogo. Se concluye que existen diferencias entre los significados de las dos generaciones, en las que los adultos mayores presentan mayor fuerza en el discurso sobre esta problemática en comparación con los adolescentes y los jóvenes. Sin embargo, el impacto del conflicto en la población joven incluye en la percepción de la realidad.

Abstract The implications of the armed conflict are dependent upon the proximity to the conflict and the unique experiences that populations have in the face of the conflict. The present study had the objective of exploring the significance of the armed conflict for 22 adolescents and youth and for 20 older adults in Bucaramanga. Using a qualitative design, a phenomenological focus, and convenience sampling, researchers carried out an in-depth interview and constructed a focus group. The results yielded categories regarding perception, knowledge, valuation, and ideas of solutions. Researchers found that older adults refer to facts regarding the conflict more often, in comparison to adolescents and youth. In relation to the valuation of the conflict, both groups perceive it as something atrocious and unjust. Both groups also noted that guerrilla groups such as the FARC, the ELN, and M-19 generated these crimes. Corruption was also highlighted within the participants' interviews. Respect to solutions to the armed conflict, dialogue stood out as a principal solution. From these results, researchers conclude that differences exist between the two generations in terms of the significance of the armed conflict. Older adults demonstrate greater strength in their interviews regarding the conflict, in comparison to adolescents and youth. However, the impact of the conflict on the youth population influences their perception of reality.

Regulation of CATSPER1 expression by the testis-determining gene SRY.

CATSPER1 gene encodes a pore-forming and pH-sensing subunit of the CatSper Ca2+- permeable channel, a protein in the flagellum essential for sperm hyperactivation. Previous studies have shown that the murine Catsper1 gene promoter is regulated by different Sox proteins. Likewise, it is acknowledged that the human CATSPER1 gene promoter sequence is enriched in potential interaction sites for the sex-determining region Y gene (SRY), which suggest a novel regulatory transcriptional mechanism for CatSper1 channel expression. Therefore, in this work, we sought to determine whether the human CATSPER1 gene expression is regulated by the SRY transcription factor. To this end, a series of deletions and mutations were introduced in the wild- type CATSPER1 gene promoter to eliminate the SRY sites, and the different constructs were tested for their ability to activate transcription in human embryonic kidney and murine spermatogonial germ cell lines (HEK-293 and GC1-spg, respectively) using luciferase assays. In addition, by using a strategy that combines electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) we investigated whether the CATSPER1 gene expression is regulated by the SRY transcription factor both in vitro and in vivo. Our results show that the transcriptional factor SRY specifically binds to different sites in the promoter sequence and has the ability to control CATSPER1 gene transcription.

Práctica clínica cotidiana frente a la evidencia científica en el manejo fisioterapéutico del dolor lumbar crónico inespecífico / Daily Clinical Practice of Scientific Evidence in the Physiotherapeutic Management of Chronic Nonspecific Low Back Pain / Prática clínica cotidiana versus a evidência científica no manejo fisioterapêutico da dor lombar crónica inespecífica

Introducción: El 80% de los adultos experimenta dolor lumbar por lo menos una vez en su vida. El dolor lumbar es la tercera causa de consulta en urgencias, la cuarta en medicina general, la segunda de pensión por invalidez y la primera de reubicación laboral. Objetivo: Comparar los criterios que orientan la toma de decisiones de un grupo de fisioterapeutas en Bogotá, Colombia para el manejo del dolor lumbar crónico inespecífico con los criterios de manejo contenidos en la guía COST B13 (European Guidelines for the Management of Chronic Non-Specific Low Back Pain, 2004). Materiales y método: Se trató de un estudio descriptivo, en el cual se seleccionó la guía de práctica clínica COST B13 para el manejo de dolor lumbar crónico inespecífico mediante la herramienta AGREE y se aplicó una encuesta a 50 fisioterapeutas por medio de un muestreo por conveniencia con el fin de comparar las prácticas clínicas que se realizan frente a las recomendaciones dadas en la guía. Resultados: El 56% de los encuestados contaba con algún tipo de entrenamiento para el manejo del dolor lumbar crónico inespecífico (DLCI). El 94% de los pacientes con DLCI atendidos oscilan en edades de 40 a 59 años, con predominio del sexo femenino. El 80% de los fisioterapeutas encuestados manifestó que la ayuda diagnóstica con la que cuentan para el manejo de los pacientes es la imagen radiológica. El 80% de los fisioterapeutas evalúa la variable de dolor lumbar experimentado por el paciente y el 54% la postura. Otros aspectos fueron reportados en menor porcentaje como test neurales, rangos de movimiento y pruebas de flexibilidad muscular. En el tratamiento del DLCI, los fisioterapeutas reportan hacer uso de los estiramientos en el 80% de los casos, la termoterapia superficial, en el 70% y el fortalecimiento muscular isométrico, en el 70%, todos con resultados favorables. Conclusión: Existen diferencias entre la práctica clínica y los lineamientos contenidos en las recomendaciones dadas por la guía COST B13 para DLCI, principalmente en los procesos de evaluación clínica, ya que suelen estar centrados en la observación y no siempre en la medición rigurosa, lo que dificulta la posibilidad de establecer indicadores de proceso y desenlace en el diagnóstico y tratamiento de los pacientes con DLCI.

Introduction: 80% of adults experience back pain at least once in their life.Back pain is the third leading cause of consultation in the emergency room, the fourth in general practice, the second of disability pension and the first job relocation. Objective: To compare criteria that guide decision making of a group of physiotherapists in Bogota, Colombia, for managing chronic nonspecific low back pain management criteria contained in the guide COST B13 (European Guidelines for the Management of Chronic Non-Specific Low Back Pain, 2004). Material and methods: This was a descriptive study, for which the clinical practice guideline COST B13 for the management of chronic nonspecific low back pain through the AGREE tool is selected. A survey was applied to 50 physiotherapists through a convenience sample to compare the clinical practices performed with the recommendations given guidance. Results: 56% of respondents had some type of training for the management of chronic nonspecific low back pain (cnlbp). 94% of attended patients with cnlbp ranged ages from 40 to 59, with female predominance. 80% of respondents stated that physiotherapists' diagnostic help with counting for the management of patients is the radiological image. 80 % of physiotherapists evaluate the variable of experienced lumbar pain based on what the patient says and 54% based on the posture. Other aspects reported rated lower percentages. In the treatment of cnlbp, physiotherapists reported the use of stretching in 80% of cases; superficial thermotherapy in 70% and isometric muscle strength in 70% of cases, all with favorable results. Conclusion: There are differences between the physiotherapists' clinical practice of and the guidelines contained in the recommendations of the in the cnlbp cost B13 guide. Mainly in the processes of physiotherapeutic assessment, as they are often focused on observation and not always in the rigorous measurement, which makes it difficult to establish process indicators and results in the diagnosis and treatment of patients with cnlbp.

Introdução: o 80% dos adultos experimenta dor lombar pelo menos uma vez em sua vida; a dor lombar é a terceira causa de consulta em emergências, a quarta em medicina geral, a segunda de pensão por invalidez e a primeira de deslocalização laboral. Objetivo: Comparar os critérios que orientam a tomada de decisões de um grupo de fisioterapeutas em Bogotá, Colômbia, para o manejo da dor lombar crónica inespecífico com os critérios de manejo conteúdos na guia COST B13 (European Guidelines for the Management of Chronic Non-Specific Low Back Pain, 2004). Materiais e métodos: tratou-se de um estudo descritivo, no qual se selecionou a guia de prática clínica COSTB 13 para o manejo de dor lombar crónico inespecífico através da ferramenta AGREE e se aplicou uma enquete a 50 fisioterapeutas através de uma amostragem por conveniência com o fim de comparar as práticas clínicas que se realizam frente às recomendações dadas na guia. Resultados: o 56% dos questionados contavam com algum tipo de treinamento para o manejo da dor lombar crónico inespecífico (DLCI). O 94% dos pacientes com DLCI atendidos oscilam em idades de 40 a 59 anos, com predomínio do sexo feminino. O 80% dos fisioterapeutas avalia a variável de dor lombar experimentado pelo paciente e o 54% a postura. Outros aspectos foram reportados em menor porcentagem como teste neurais, rasgos de movimentos, e provas de flexibilidade muscular. No tratamento da DLCI, os fisioterapeutas reportam fazer uso dos estiramentos no 80% dos casos, a termoterapia superficial no 70% e o fortalecimento muscular isométrico no 70%, todos com resultados favoráveis. Conclusões: Existem diferenças entre a prática clínica e os lineamentos conteúdos nas recomendações dadas pela guia COST B12 para DLCI principalmente nos processos de avaliação clínica devido a que costumam estar centrados na observação e não sempre na medição rigorosa o que dificulta a possibilidade de estabelecer indicadores de processo e desenlace no diagnóstico e tratamento dos pacientes com DLCI.

Possible involvement of the sco2127 gene product in glucose repression of actinorhodin production in Streptomyces coelicolor.

Streptomyces coelicolor mutants resistant to 2-deoxyglucose are insensitive to carbon catabolite repression (CCR). Total reversion to CCR sensitivity is observed by mutant complementation with a DNA region harboring both glucose kinase glkA gene and the sco2127 gene. The sco2127 is located upstream of glkA and encodes a putative protein of 20.1 kDa. In S. coelicolor, actinorhodin production is subject to glucose repression. To explore the possible involvement of both SCO2127 and glucose kinase (Glk) in the glucose sensitivity of actinorhodin production, this effect was evaluated in a wild-type S. coelicolor A3(2) M145 strain and a sco2127 null mutant (Δsco2127) derived from this wild-type strain. In comparison with strain M145, actinorhodin production by the mutant was insensitive to glucose repression. Under repressive conditions, only minor differences were observed in glucose utilization and Glk production between these strains. SCO2127 was detected mainly during the first 36 h of fermentation, just before the onset of antibiotic production, and its synthesis was not related to a particular carbon source. The glucose sensitivity of antibiotic production was restored to wild-type phenotype by transformation with an integrative plasmid containing sco2127. Our results support the hypothesis that SCO2127 is a negative regulator of actinorhodin production and suggest that the effect is independent of Glk.

Interaction of SCO2127 with BldKB and its possible connection to carbon catabolite regulation of morphological differentiation in Streptomyces coelicolor.

In Streptomyces coelicolor, the sco2127 gene is located upstream of the gene encoding for glucose kinase. This region restores sensitivity to carbon catabolite repression (CCR) of Streptomyces peucetius var. caesius mutants, resistant to 2-deoxyglucose (Dog(R)). In order to search for the possible mechanisms behind this effect, sco2127 was overexpressed and purified for protein-protein interaction studies. SCO2127 was detected during the late growth phase of S. coelicolor grown in a complex media supplemented with 100 mM glucose. Pull-down assays using crude extracts from S. coelicolor grown in the same media, followed by far-western blotting, allowed detection of two proteins bound to SCO2127. The proteins were identified by MALDI-TOF mass spectrometry as SCO5113 and SCO2582. SCO5113 (BldKB) is a lipoprotein ABC-type permease (∼66 kDa) involved in mycelium differentiation by allowing the transport of the morphogenic oligopeptide Bld261. SCO2582, is a putative membrane metalloendopeptidase (∼44 kDa) of unknown function. In agreement with the possible role of SCO2127 in mycelium differentiation, delayed aerial mycelium septation and sporulation was observed when S. coelicolor A3(2) was grown in the presence of elevated glucose concentrations (100 mM), an effect not seen in a Δ-sco2127 mutant derived from it. We speculate that SCO2127 might represent a key factor in CCR of mycelium differentiation by interacting with BldKB.

Carbon source regulation of antibiotic production.

Antibiotics are low-molecular-mass products of secondary metabolism, nonessential for the growth of producing organisms, but very important for human health. They have unusual structures and are most often formed during the late growth phase of the producing microorganisms. Their production arises from intracellular intermediates, which are condensed into more complex structures through defined biochemical pathways. Their synthesis can be influenced by manipulating the type and concentration of nutrients formulating the culture media. Among them, the effect of the carbon source has been the subject of continuous studies for both industry and research groups. Glucose and other carbohydrates have been reported to interfere with antibiotic synthesis and this effect depends on the rapid utilization of the preferred carbon source. Different mechanisms have been described in bacteria and fungi to explain the negative effects of carbon catabolites on antibiotic production. They show important differences depending on the microbe being considered. Their understanding and manipulation have been useful for both perfecting fermentation conditions to produce anti-infectives and for strain improvement. To improve the production of antibiotics, carbon source repression can be decreased or abolished by mutations resulting in antimetabolite resistance. Enzymes reported as regulated by the carbon source have been used as targets for strain improvement. During the last few years, important advances have been reported elucidating the essential aspects of carbon source regulation on antibiotic production at biochemical and molecular levels. The aim of this review is to describe these advances, giving special emphasis to those reported for the genus Streptomyces.

Production of microbial secondary metabolites: regulation by the carbon source.

Microbial secondary metabolites are low molecular mass products, not essential for growth of the producing cultures, but very important for human health. They include antibiotics, antitumor agents, cholesterol-lowering drugs, and others. They have unusual structures and are usually formed during the late growth phase of the producing microorganisms. Its synthesis can be influenced greatly by manipulating the type and concentration of the nutrients formulating the culture media. Among these nutrients, the effect of the carbon sources has been the subject of continuous studies for both, industry and research groups. Different mechanisms have been described in bacteria and fungi to explain the negative carbon catabolite effects on secondary metabolite production. Their knowledge and manipulation have been useful either for setting fermentation conditions or for strain improvement. During the last years, important advances have been reported on these mechanisms at the biochemical and molecular levels. The aim of the present review is to describe these advances, giving special emphasis to those reported for the genus Streptomyces.