Repurposing Antimalarial Pyronaridine as a DNA Repair Inhibitor to Exploit the Full Potential of Gold-Nanoparticle-Mediated Radiation Response.

Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors. The objective of this study was to explore the repurposing of an antimalarial drug, pyronaridine (PYD), as a DNA repair inhibitor to further enhance RT/GNP-induced DNA damage in cancerous cell lines. We were able to achieve inhibitory effects of DNA repair due to PYD at 500 nM concentration. Our results show a significant enhancement in DNA double-strand breaks of 42% in HeLa cells treated with PYD/GNP/RT in comparison to GNP/RT alone when irradiated with a dose of 2 Gy. Furthermore, there was a significant reduction in cellular proliferation for both HeLa and HCT-116 irradiated cells with the combined treatment of PYD/GNP/RT. Therefore, the emergence of promising novel concepts introduced in this study could lay the foundation for the transition of this treatment modality into clinical environments.

Modulation of ERCC1-XPF Heterodimerization Inhibition via Structural Modification of Small Molecule Inhibitor Side-Chains.

Inhibition of DNA repair enzymes is an attractive target for increasing the efficacy of DNA damaging chemotherapies. The ERCC1-XPF heterodimer is a key endonuclease in numerous single and double strand break repair processes, and inhibition of the heterodimerization has previously been shown to sensitize cancer cells to DNA damage. In this work, the previously reported ERCC1-XPF inhibitor 4 was used as the starting point for an in silico study of further modifications of the piperazine side-chain. A selection of the best scoring hits from the in silico screen were synthesized using a late stage functionalization strategy which should allow for further iterations of this class of inhibitors to be readily synthesized. Of the synthesized compounds, compound 6 performed the best in the in vitro fluorescence based endonuclease assay. The success of compound 6 in inhibiting ERCC1-XPF endonuclease activity in vitro translated well to cell-based assays investigating the inhibition of nucleotide excision repair and disruption of heterodimerization. Subsequently compound 6 was shown to sensitize HCT-116 cancer cells to treatment with UVC, cyclophosphamide, and ionizing radiation. This work serves as an important step towards the synergistic use of DNA repair inhibitors with chemotherapeutic drugs.

Inhibition of triple negative breast cancer metastasis and invasiveness by novel drugs that target epithelial to mesenchymal transition.

Invasive breast cancer (BrCa) is predicted to affect 1 in 9 women in a lifetime;1 in 32 will die from this disease. The most aggressive forms of BrCa, basal-like/triple-negative phenotype (TNBC), are challenging to treat and result in higher mortality due high number of metastatic cases. There is a paucity of options for TNBC treatment, which highlights the need for additional innovative treatment approaches. NIH-III mice were injected in the abdominal mammary fat pad with luciferase-expressing derivative of the human TNBC cell line, MDA-MB-231 cells. Animals were gavage-fed with nitrofen at the doses of 1, 3 or 6 mg/kg/alternate days. However, several structural properties/components of nitrofen raise concerns, including its high lipophilicity (cLogP of nearly 5) and a potential toxophore in the form of a nitroarene group. Therefore, we developed analogues of nitrofen which lack the nitro group and/or have replaced the diaryl ether linker with a diarylamine that could allow modulation of polarity. In vitro anti-invasiveness activity of nitrofen analogues were evaluated by quantitative determination of invasion of MDA-MB-231-Luciferase cells through Matrigel using a Boyden chamber. Our in vivo data show that nitrofen efficiently blocks TNBC tumor metastasis. In vitro data suggest that this is not due to cytotoxicity, but rather is due to impairment of invasive capacity of the cells. Further, using an in vitro model of EMT, we show that nitrofen interferes with the process of EMT and promotes mesenchymal to epithelial transformation. In addition, we show that three of the nitrofen analogues significantly reduced invasive potential of TNBC cells, which may, at least partially, be attributed to the analogues' ability to promote mesenchymal to epithelial-like transformation of TNBC cells. Our study shows that nitrofen, and more importantly its analogues, are significantly effective in limiting the invasive potential of TNBC cell lines with minimal cytotoxic effect. Further, we demonstrate that nitrofen its analogues, are very effective in reversing mesenchymal phenotype to a more epithelial-like phenotype. This may be significant for the treatment of patients with mesenchymal-TNBC tumor subtype who are well known to exhibit high resistance to chemotherapy.

Evolving tides aggravate nuisance flooding along the U.S. coastline.

Nuisance flooding (NF) is defined as minor, nondestructive flooding that causes substantial, accumulating socioeconomic impacts to coastal communities. While sea-level rise is the main driver for the observed increase in NF events in the United States, we show here that secular changes in tides also contribute. An analysis of 40 tidal gauge records from U.S. coasts finds that, at 18 locations, NF increased due to tidal amplification, while decreases in tidal range suppressed NF at 11 locations. Estuaries show the largest changes in NF attributable to tide changes, and these can often be traced to anthropogenic alterations. Limited long-term measurements from estuaries suggest that the effects of evolving tides are more widespread than the locations considered here. The total number of NF days caused by tidal changes has increased at an exponential rate since 1950, adding ~27% to the total number of NF events observed in 2019 across locations with tidal amplification.

Design, synthesis and in vitro cell-free/cell-based biological evaluations of novel ERCC1-XPF inhibitors targeting DNA repair pathway.

The structure-specific ERCC1-XPF endonuclease is essential for repairing bulky DNA lesions and helix distortions induced by UV radiation, which forms cyclobutane pyrimidine dimers (CPDs), or chemicals that crosslink DNA strands such as cyclophosphamide and platinum-based chemotherapeutic agents. Inhibition of the ERCC1-XPF endonuclease activity has been shown to sensitize cancer cells to these chemotherapeutic agents. In this study, we have conducted a structure activity relationship analysis based around the previously identified hit compound, 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-methylpiperazin1-yl)methyl)phenol (F06), as a reference compound. Three different series of compounds have been rationally designed and successfully synthesized through various modifications on three different sites of F06 based on the corresponding suggestions of the previous pharmacophore model. The in vitro screening results revealed that 2-chloro-9-((3-((4-(2-(dimethylamino)ethyl)piperazin-1-yl)methyl)-4-hydroxyphenyl)amino)acridin-2-ol (B9) has a potent inhibitory effect on the ERCC1-XPF activity (IC50 = 0.49 µM), showing 3-fold improvement in inhibition activity compared to F06. In addition, B9 not only displayed better binding affinity to the ERCC1-XPF complex but also had the capacity to potentiate the cytotoxicity effect of UV radiation and inhibiting the nucleotide excision repair, by the inhibition of removal of CPDs, and cyclophosphamide toxicity to colorectal cancer cells.

Computer-aided drug design of small molecule inhibitors of the ERCC1-XPF protein-protein interaction.

The heterodimer of DNA excision repair protein ERCC-1 and DNA repair endonuclease XPF (ERCC1-XPF) is a 5'-3' structure-specific endonuclease essential for the nucleotide excision repair (NER) pathway, and it is also involved in other DNA repair pathways. In cancer cells, ERCC1-XPF plays a central role in repairing DNA damage induced by chemotherapeutics including platinum-based and cross-linking agents; thus, its inhibition is a promising strategy to enhance the effect of these therapies. In this study, we rationally modified the structure of F06, a small molecule inhibitor of the ERCC1-XPF interaction (Molecular Pharmacology, 84, 2013 and 12), to improve its binding to the target. We followed a multi-step computational approach to investigate potential modification sites of F06, rationally design and rank a library of analogues, and identify candidates for chemical synthesis and in vitro testing. Our top compound, B5, showed an improved half-maximum inhibitory concentration (IC50 ) value of 0.49 µM for the inhibition of ERCC1-XPF endonuclease activit, and lays the foundation for further testing and optimization. Also, the computational approach reported here can be used to develop DNA repair inhibitors targeting the ERCC1-XPF complex.

Changing Tides: The Role of Natural and Anthropogenic Factors.

Tides are changing worldwide at rates not explained by astronomical forcing. Rather, the observed evolution of tides and other long waves, such as storm surges, is influenced by shelf processes and changes to the roughness, depth, width, and length of embayments, estuaries, and tidal rivers. In this review, we focus on processes in estuaries and tidal rivers, because that is where the largest changes to tidal properties are occurring. Recent literature shows that changes in tidal amplitude have been ubiquitous worldwide over the past century, often in response to wetland reclamation, channel dredging, and other environmental changes. While tidal amplitude changes are sometimes slight (<1%) or even negative, we identify two types of systems that are particularly prone to tidal amplification: (a) shallow, strongly damped systems, in which a small increase in depth produces a large decrease in effective friction, and (b) systems in which wave reflection and resonance are strongly influenced by changes to depth, friction, and convergence. The largest changes in amplitude occur inland, some distance from the coast, and can sometimes be measured in meters. Tide changes are a leading indicator that the dynamics of storm surges and river flood waves have also changed and are often associated with shifts in sediment transport, salinity intrusion, and ecosystem properties. Therefore, the dynamics of tidal evolution have major implications for coastal management, particularly for systems that are sensitive to changes in geometry induced by sea-level rise and anthropogenic development.

Targeting DNA Repair in Tumor Cells via Inhibition of ERCC1-XPF.

The ERCC1-XPF heterodimer is a 5'-3' structure-specific endonuclease, which plays an essential role in several DNA repair pathways in mammalian cells. ERCC1-XPF is primarily involved in the repair of chemically induced helix-distorting and bulky DNA lesions, such as cyclobutane pyrimidine dimers (CPDs), and DNA interstrand cross-links. Inhibition of ERCC1-XPF has been shown to potentiate cytotoxicity of platinum-based drugs and cyclophosphamide in cancer cells. In this study, the previously described ERCC1-XPF inhibitor 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-methylpiperazin-1-yl)methyl)phenol (compound 1) was used as a reference compound. Following the outcome of docking-based virtual screening (VS), we synthesized seven novel derivatives of 1 that were identified in silico as being likely to have high binding affinity for the ERCC1-XPF heterodimerization interface by interacting with the XPF double helix-hairpin-helix (HhH2) domain. Two of the new compounds, 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-cyclohexylpiperazin-1-yl)methyl)phenol (compound 3) and 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-(2-(dimethylamino)ethyl) piperazin-1-yl) methyl) phenol (compound 4), were shown to be potent inhibitors of ERCC1-XPF activity in vitro. Compound 4 showed significant inhibition of the removal of CPDs in UV-irradiated cells and the capacity to sensitize colorectal cancer cells to UV radiation and cyclophosphamide.

Age Is a Greater Influence on Small Saccades Than Target Size in Normal Subjects on the Horizontal Video Head Impulse Test.

Objective: This study sought to investigate whether the size of the target used in the horizontal vHIT has an effect on the saccade profile of healthy subjects, and to expand upon previous work linking age to the existence of small vHIT saccades. Methods: Forty eight participants were recruited between 18 and 77 years of age, with no history of vestibular, oculomotor or neurological conditions and a visual acuity of at least 0.3 LogMAR. Participants underwent four consecutive horizontal vHIT trials using the standard target size and three smaller targets. VOR gain and metrics for saccadic incidence, peak eye velocity and latency were then extracted from results. Results: Target size was a statistically significant influence on saccade metrics. As target size increased, saccadic incidence decreased while peak eye velocity and latency increased. However, a potential order effect was also discovered, and once this was corrected for the remaining effect of target size was small and is likely clinically insignificant. The effect of age was much stronger than target size; increasing age was strongly positively correlated with saccadic incidence and showed a medium size correlation with peak velocity, though not with saccadic latency. Conclusion: While this study suggests that target size may have a statistically significant impact on the vHIT saccade profile of normal subjects, age has a greater influence on the incidence and size of small vHIT saccades.

Coupling of sea level and tidal range changes, with implications for future water levels.

Are perturbations to ocean tides correlated with changing sea-level and climate, and how will this affect high water levels? Here, we survey 152 tide gauges in the Pacific Ocean and South China Sea and statistically evaluate how the sum of the four largest tidal constituents, a proxy for the highest astronomical tide (HAT), changes over seasonal and interannual time scales. We find that the variability in HAT is significantly correlated with sea-level variability; approximately 35% of stations exhibit a greater than ±50 mm tidal change per meter sea-level fluctuation. Focusing on a subset of three stations with long records, probability density function (PDF) analyses of the 95% percentile exceedance of total sea level (TSL) show long-term changes of this high-water metric. At Hong Kong, the increase in tides significantly amplifies the risk caused by sea-level rise. Regions of tidal decrease and/or amplification highlight the non-linear response to sea-level variations, with the potential to amplify or mitigate against the increased flood risk caused by sea-level rise. Overall, our analysis suggests that in many regions, local flood level determinations should consider the joint effects of non-stationary tides and mean sea level (MSL) at multiple time scales.

Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.

Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation.

The future of biologics: applications for food allergy.

Allergic diseases affect millions worldwide, with growing evidence of an increase in allergy occurrence over the past few decades. Current treatments for allergy include corticosteroids to reduce inflammation and allergen immunotherapy; however, some subjects experience treatment-resistant inflammation or adverse reactions to these treatments, and there are currently no approved therapeutics for the treatment of food allergy. There is a dire need for new therapeutic approaches for patients with poorly controlled atopic diseases and a need to improve the safety and effectiveness of allergen immunotherapy. Improved understanding of allergy through animal models and clinical trials has unveiled potential targets for new therapies, leading to the development of several biologics to treat allergic diseases. This review focuses on the mechanisms that contribute to allergy, with an emphasis on future targets for biologics for the treatment of food allergy. These biologics include immunotherapy with novel anti-IgE antibodies and analogs, small-molecule inhibitors of cell signaling, anti-type 2 cytokine mAbs, and TH1-promoting adjuvants.

The evolution of allergen and non-specific immunotherapy: past achievements, current applications and future outlook.

Recent epidemiological studies estimated that more than 30% of European suffer from allergic rhinitis or conjunctivitis, while up to 20% suffer from asthma and 15% from allergic skin conditions, while for many other regions the prevalence is increasing. Allergen immunotherapy represents the only available treatment that can modify the allergic disease process, and thus is worth considering as a treatment in affected individuals. A beneficial effect of allergen immunotherapy has been shown in both adults and children affected by allergic rhinitis, allergic conjunctivitis, allergic asthma and hymenoptera venom allergy. The present study represents an overview on allergen immunotherapy, focusing on the principal aspects of the use of immunotherapy in the past, its recent clinical applications and future outlook.

Immune mechanisms of sublingual immunotherapy.

Sublingual immunotherapy (SLIT) is a well-established allergen-specific immunotherapy and a safe and effective strategy to reorient inappropriate immune responses in allergic patients. SLIT takes advantage of the tolerogenic environment of the oral mucosa to promote tolerance to the allergen. Several clinical studies have investigated the complex interplay of innate and adaptive immune responses that SLIT exploits. The oral immune system is composed of tolerogenic dendritic cells that, following uptake of allergen during SLIT, support the differentiation of T helper cell type 1 (Th1) and the induction of IL-10-producing regulatory T cells. Following SLIT, allergic disease-promoting T helper cell type 2 (Th2) responses shift to a Th1 inflammatory response, and IL-10 and transforming growth factor (TGF)-ß production by regulatory T cells and tolerogenic dendritic cells suppress allergen-specific T cell responses. These immune changes occur both in the sublingual mucosa and in the periphery of a patient following SLIT. SLIT also promotes the synthesis of allergen-specific IgG and IgA antibodies that block allergen-IgE complex formation and binding to inflammatory cells, thus encouraging an anti-inflammatory environment. Several of these revealing findings have also paved the way for the identification of biomarkers of the clinical efficacy of SLIT. This review presents the emerging elucidation of the immune mechanisms mediated by SLIT.

Dynamic functional modulation of CD4+ T cell recall responses is dependent on the inflammatory environment of the secondary stimulus.

The parameters that modulate the functional capacity of secondary Th1 effector cells are poorly understood. In this study, we employ a serial adoptive transfer model system to show that the functional differentiation and secondary memory potential of secondary CD4+ effector T cells are dependent on the inflammatory environment of the secondary challenge. Adoptive transfer of TCR transgenic lymphocytic choriomeningitis virus (LCMV) Glycoprotein-specific SMARTA memory cells into LCMV-immune hosts, followed by secondary challenge with Listeria monocytogenes recombinantly expressing a portion of the LCMV Glycoprotein (Lm-gp61), resulted in the rapid emergence of SMARTA secondary effector cells with heightened functional avidity (as measured by their ability to make IFNγ in response to ex vivo restimulation with decreasing concentrations of peptide), limited contraction after pathogen clearance and stable maintenance secondary memory T cell populations. In contrast, transfer of SMARTA memory cells into naïve hosts prior to secondary Lm-gp61 challenge, which resulted in a more extended infectious period, resulted in poor functional avidity, increased death during the contraction phase and poor maintenance of secondary memory T cell populations. The modulation of functional avidity during the secondary Th1 response was independent of differences in antigen load or persistence. Instead, the inflammatory environment strongly influenced the function of the secondary Th1 response, as inhibition of IL-12 or IFN-I activity respectively reduced or increased the functional avidity of secondary SMARTA effector cells following rechallenge in a naïve secondary hosts. Our findings demonstrate that secondary effector T cells exhibit inflammation-dependent differences in functional avidity and memory potential, and have direct bearing on the design of strategies aimed at boosting memory T cell responses.

Bim mediates the elimination of functionally unfit Th1 responders from the memory pool.

Selective clonal deletion in the CD4(+) T cell compartment during the transition from effector to memory is accompanied by enhanced expression of the pro-apoptotic Bcl-2 family member Bim. Here, we show that Bim deficiency enables the survival of poorly functional Th1 responders that are normally eliminated during contraction. However, rescued bim(-/-) CD4(+) "memory" T cells continued to demonstrate deficient effector functions, poor sensitivity to antigen and an inability to respond to secondary challenge. Our results demonstrate that Bim activity plays a key role in shaping the CD4(+) memory T cell repertoire, ensuring the emergence of highly functional CD4(+) memory T cells and the elimination of Th1 effector cells with sub-optimal function. We propose that Bim is a key mediator of T cell death in the absence of appropriate TCR-driven activation and differentiation.

Stability and function of secondary Th1 memory cells are dependent on the nature of the secondary stimulus.

Following acute infection in some mouse models, CD4+ memory T cells steadily decline over time. Conversely, in humans, CD4+ memory T cells can be maintained for many years at levels similar to CD8+ T cells. Because we previously observed that the longevity of Th1 memory cell survival corresponded to their functional avidity, we hypothesized that secondary challenge, which enriches for high functional avidity Th1 responders, would result in more stable Th1 memory populations. We found that following a heterologous secondary challenge, Th1 memory cells were maintained at stable levels compared with primary Th1 memory cells, showing little to no decline after day 75 postinfection. The improved stability of secondary Th1 memory T cells corresponded to enhanced homeostatic turnover; enhanced trafficking of effector memory Th1 cells to tissue sites of infection, such as the liver; and acquisition or maintenance of high functional avidity following secondary challenge. Conversely, a weaker homologous rechallenge failed to induce a stable secondary Th1 memory population. Additionally, homologous secondary challenge resulted in a transient loss of functional avidity by Th1 memory cells recruited into the secondary response. Our findings suggest that the longevity of Th1 memory T cells is dependent, at least in part, on the combined effects of primary and secondary Ag-driven differentiation. Furthermore, they demonstrate that the quality of the secondary challenge can have profound effects on the longevity and function of the ensuing secondary Th1 memory population.

An MHC class Ib-restricted CD8+ T cell response to lymphocytic choriomeningitis virus.

Conventional MHC class Ia-restricted CD8(+) T cells play a dominant role in the host response to virus infections, but recent studies indicate that T cells with specificity for nonclassical MHC class Ib molecules may also participate in host defense. To investigate the potential role of class Ib molecules in anti-viral immune responses, K(b-/-)D(b-/-)CIITA(-/-) mice lacking expression of MHC class Ia and class II molecules were infected with lymphocytic choriomeningitis virus (LCMV). These animals have a large class Ib-selected CD8(+) T cell population and they were observed to mediate partial (but incomplete) virus clearance during acute LCMV infection as compared with K(b-/-)D(b-/-)ß(2)-microglobulin(-/-) mice that lack expression of both MHC class Ia and class Ib molecules. Infection was associated with expansion of splenic CD8(+) T cells and induction of granzyme B and IFN-γ effector molecules in CD8(+) T cells. Partial virus clearance was dependent on CD8(+) cells. In vitro T cell restimulation assays demonstrated induction of a population of ß(2)-microglobulin-dependent, MHC class Ib-restricted CD8(+) T cells with specificity for viral Ags and yet to be defined nonclassical MHC molecules. MHC class Ib-restricted CD8(+) T cell responses were also observed after infection of K(b-/-)D(b-/-)mice despite the low number of CD8(+) T cells in these animals. Long-term infection studies demonstrated chronic infection and gradual depletion of CD8(+) T cells in K(b-/-)D(b-/-)CIITA(-/-) mice, demonstrating that class Ia molecules are required for viral clearance. These findings demonstrate that class Ib-restricted CD8(+) T cells have the potential to participate in the host immune response to LCMV.

Piroxicam and meloxicam ameliorate hepatic oxidative stress and protein carbonylation in Kupffer and sinusoidal endothelial cells promoted by ischemia-reperfusion injury.

The present study was aimed to assess the effect of protein carbonylation (PC) in hepatic cells and effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on indicators of tissue damage induced by liver ischemia-reperfusion injury (LIRI). Warm ischemia was performed by partial vascular occlusion during 90 min in Wistar rats. In serum, we determined the catalytic activity of Alanine Aminotransferase, Aspartate Aminotransferase, Lacticate Dehydrogenase, and Ornithine Carbamoyltransferase. In liver samples, we studied cellular alterations by means of histologic studies, lipid peroxidation, PC by immunohistochemistry, apoptosis and reactive oxygen species in bile by electron paramagnetic resonance. Based on PC data, sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were the first to exhibit LIRI-associated oxidative damage and prior to parenchymal cells. Administration of piroxicam or meloxicam during the pre-ischemic period produced a highly significant decrease in all studied injury indicators. No significant differences were revealed between the protective action of the two drugs. The data shown here suggest the potential use of NSAIDs such as piroxicam or meloxicam in minimizing ischemic event-caused damage in liver. We also propose that PC may be employed as an adequate tool to assess tissue damage after oxidative stress.

Actividad antimicrobiana de bacterias marinas aisladas del Golfo de México / Antimicrobial activity of marine bacteria isolated from Gulf of Mexico

Currently there is a need for new antibiotics with an alternative mode of action and new chemical structures. Bacterial pathogens are gradually becoming more resistant to conventional antibiotics, generating an emergence of infectious diseases and they are becoming a great problem in the field of public health. In this study, seven different isolated bacteria were obtained from offshore seawater and sediment of the Gulf of Mexico from Campeche, Mexico. They were substance producers which inhibit growth of human pathogens like Staphylococcus aureus and Pseudomonas aeruginosa and one of them was a polymer producer on peptone and glucose culture. They were characterized phenotipically by means of morphological techniques and physiologically by conventional tests. Four of them were Gram-positive bacteria and the Scanning Electron Microscope analysis revealed their size between 0.6 – 1.5 µm. One of seven marine strains, Gram negative, yellow pigmented, slightly curved rods, was identified as Pseudoalteromonas sp. on the analysis of the gen16S rRNA sequence.

Hoy en día existe la necesidad de encontrar antibióticos con nuevas estructuras químicas y modos de acción alternativos. Se ha observado que bacterias patógenas comunes progresivamente desarrollan resistencia al tratamiento con antibióticos tradicionales, surgiendo y resurgiendo enfermedades infecciosas que generan un gran problema en salud pública. En este estudio, se obtuvieron siete colonias bacterianas pigmentadas de agua de mar y de sedimento marino procedente de las costas de Campeche, México. Las colonias aisladas produjeron sustancias que inhibieron el crecimiento de bacterias patógenas a humanos como Staphylococcus aureus and Pseudomonas aeruginosa. Las bacterias marinas fueron caracterizadas fenotípicamente de acuerdo a su morfología microscópica y por pruebas fisiológicas convencionales. Cuatro de los aislados resultaron ser bacterias Gram positivas y las otras tres fueron Gram negativas. Cuando se observaron por microscopía electrónica de barrido, su tamaño aproximado fue entre 0,6 – 1,5 µm. Uno de los aislados fue una colonia amarilla con bacilos cortos Gram negativos y ligeramente curvos, identificado por la secuencia del gen16S rRNA como Pseudoalteromonas sp.