Bacterial Pathogens: Potential Source For Antimicrobial Peptides.

As more antibiotics become ineffective due to drug-resistant bacteria, alternative therapies for infections must be prioritized. While pathogenic bacteria are a major threat, they also supply a massive reservoir of potential drugs for treating a wide range of illnesses. The concerning emergence of antimicrobial resistance and the rapidly dwindling therapeutic pipeline need the quick discovery and development of new antibiotics. Despite their great promise for natural product medicine development, pathogenic microorganisms have remained mostly unexplored and understudied. We review the antibacterial activity of specialized metabolites derived from pathogenic bacteria, emphasizing those presently in pre-clinical studies or with promise for medication development. Several atypical biosynthetic pathways are outlined, together with the crucial functions. We also discuss the mechanism of action and antibacterial activities of the antibiotics under consideration. Pathogenic bacteria as a rich source of antibiotics, along with recent advances in genomics and natural product research methods, may usher in a new golden age of antibiotic discovery.

Crassaminicella profunda gen. nov., sp. nov., an anaerobic marine bacterium isolated from deep-sea sediments.

A novel, anaerobic, chemo-organotrophic bacterium, designated strain Ra1766H(T), was isolated from sediments of the Guaymas basin (Gulf of California, Mexico) taken from a depth of 2002  m. Cells were thin, motile, Gram-stain-positive, flexible rods forming terminal endospores. Strain Ra1766H(T) grew at temperatures of 25-45 °C (optimum 30 °C), pH 6.7-8.1 (optimum 7.5) and in a salinity of 5-60 g l(-1) NaCl (optimum 30 g l(-1)). It was an obligate heterotrophic bacterium fermenting carbohydrates (glucose and mannose) and organic acids (pyruvate and succinate). Casamino acids and amino acids (glutamate, aspartate and glycine) were also fermented. The main end products from glucose fermentation were acetate, butyrate, ethanol, H2 and CO2. Sulfate, sulfite, thiosulfate, elemental sulfur, fumarate, nitrate, nitrite and Fe(III) were not used as terminal electron acceptors. The predominant cellular fatty acids were C14  : 0, C16 : 1ω7, C16 : 1ω7 DMA and C16 : 0. The main polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and phospholipids. The G+C content of the genomic DNA was 33.7 mol%. Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain Ra1766H(T) was affiliated to cluster XI of the order Clostridiales, phylum Firmicutes. The closest phylogenetic relative of Ra1766H(T) was Geosporobacter subterraneus (94.2% 16S rRNA gene sequence similarity). On the basis of phylogenetic inference and phenotypic properties, strain Ra1766H(T) ( = DSM 27501(T) = JCM 19377(T)) is proposed to be the type strain of a novel species of a novel genus, named Crassaminicella profunda.

Vallitalea guaymasensis gen. nov., sp. nov., isolated from marine sediment.

A novel obligately anaerobic, non-spore-forming, rod-shaped mesophilic, halophilic, Gram-stain-negative bacterium, was isolated from sediments of Guaymas Basin. The strain, designated Ra1766G1(T), grew at 20-40 °C (optimum, 30-35 °C) and at pH 6.0-8.0 (optimum, pH 6.5-7.5). It required 0.5-7.5 % NaCl (optimum, 2-3 %) for growth. Sulfate, thiosulfate, elemental sulfur, sulfite, fumarate, nitrate and nitrite were not used as terminal electron acceptors. Strain Ra1766G1(T) used cellobiose, glucose, mannose, maltose, arabinose, raffinose, galactose, ribose, sucrose, pyruvate and xylose as electron donors. The main fermentation product from glucose metabolism was acetate. The predominant cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0, anteiso DMA-C15 : 0 and C16 : 0. The main polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, iso-DMA-C15 : 0 glycolipids and phospholipids. The G+C content of the genomic DNA was 31.2 mol%. The closest phylogenetic relatives of strain Ra1766G1(T) were Natranaerovirga pectinivora AP3(T) (92.4 % 16S rRNA gene sequence similarity), Natranaerovirga hydrolytica APP2(T)(90.2 %) and Defluviitalea saccharophila 6LT2(T) (88.9 %). On the basis of phylogenetic inference and phenotypic properties, strain Ra1766G1(T) represents a novel species of a new genus for which the name Vallitalea guaymasensis is proposed. The type strain of the type species is Ra1766G1(T) ( = DSM 24848(T) = JCM17997(T)).

Oxygen uptake rates in the hyperthermophilic anaerobe Thermotoga maritima grown in a bioreactor under controlled oxygen exposure: clues to its defence strategy against oxidative stress.

A 2.3-L bioreactor was specially adapted to grow hyperthermophilic microorganisms under controlled conditions of temperature, pH, redox potential and dissolved O(2). Using this bioreactor regulated at 80°C and pH 7.0, we demonstrated that Thermotoga maritima recovered its growth despite being exposed to oxygen for a short time (30 min with a maximum concentration of 23 µM of dissolved oxygen). Under these conditions, we demonstrated that O(2) uptake rate, estimated at 73.6 µmoles O(2) min(-1) g proteins(-1) for dissolved oxygen, was optimal and constant, when dissolved oxygen was present in a range of 22-5 µM. Transcription analyses revealed that during short oxygen exposure, T. maritima expressed genes coding for enzymes to deal with O(2) and reactive oxygen species (ROS) such as peroxides. Thus, genes encoding ROS-scavenging systems, alkyl hydroperoxide reductase (ahp), thioredoxin-dependent thiol peroxidase (bcp 2) and to a lesser extent neelaredoxin (nlr) and rubrerythrin (rbr), were found to be upregulated during oxygen exposure. The oxygen reductase FprA, homologous to the rubredoxin-oxygen oxidoreductase (ROO) found in Desulfovibrio species, is proposed as a primary consumer of O(2) in T. maritima. Moreover, the expression of frpA was shown to depend on the redox (Eh) level of the culture medium.

Effect of Oxygen and Redox Potential on Glucose Fermentation in Thermotoga maritima under Controlled Physicochemical Conditions.

Batch cultures of Thermotoga maritima were performed in a bioreactor equipped with instruments adapted for experiments performed at 80°C to mimic the fluctuating oxidative conditions in the hot ecosystems it inhabits. When grown anaerobically on glucose, T. maritima was shown to significantly decrease the redox potential (Eh) of the culture medium down to about -480 mV, as long as glucose was available. Addition of oxygen into T. maritima cultures during the stationary growth phase led to a drastic reduction in glucose consumption rate. However, although oxygen was toxic, our experiment unambiguously proved that T. maritima was able to consume it during a 12-hour exposure period. Furthermore, a shift in glucose metabolism towards lactate production was observed under oxidative conditions.