Staphylococcus aureus is clearly the most pathogenic member of the Staphylococcaceae. This is in large part due to the acquisition of an impressive arsenal of virulence factors that are coordinately regulated by a series of dedicated transcription factors. What is becoming more and more appreciated in the field is the influence of the metabolic state of S. aureus on the activity of these virulence regulators and their roles in modulating metabolic gene expression. Here I highlight recent advances in S. aureus metabolism as it pertains to virulence. Specifically, mechanisms of nutrient acquisition are outlined including carbohydrate and non-carbohydrate carbon/energy sources as well as micronutrient (Fe, Mn, Zn and S) acquisition. Additionally, energy producing strategies (respiration versus fermentation) are discussed and put in the context of pathogenesis. Finally, transcriptional regulators that coordinate metabolic gene expression are outlined, particularly those that affect the activities of major virulence factor regulators. This chapter essentially connects many recent observations that link the metabolism of S. aureus to its overall pathogenesis and hints that the mere presence of a plethora of virulence factors may not entirely explain the extraordinary pathogenic potential of S. aureus.

Virulence and Metabolism.

Pathogens give rise to a wide range of diseases threatening global health and hence drawing public health agencies' attention to establish preventative and curative solutions. Genome-scale metabolic modeling is ever increasingly used tool for biomedical applications including the elucidation of antibiotic resistance, virulence, single pathogen mechanisms and pathogen-host interaction systems. With this approach, the sophisticated cellular system of metabolic reactions inside the pathogens as well as between pathogen and host cells are represented in conjunction with their corresponding genes and enzymes. Along with essential metabolic reactions, alternate pathways and fluxes are predicted by performing computational flux analyses for the growth of pathogens in a very short time. The genes or enzymes responsible for the essential metabolic reactions in pathogen growth are regarded as potential drug targets, as a priori guide to researchers in the pharmaceutical field. Pathogens alter the key metabolic processes in infected host, ultimately the objective of these integrative constraint-based context-specific metabolic models is to provide novel insights toward understanding the metabolic basis of the acute and chronic processes of infection, revealing cellular mechanisms of pathogenesis, identifying strain-specific biomarkers and developing new therapeutic approaches including the combination drugs. The reaction rates predicted during different time points of pathogen development enable us to predict active pathways and those that only occur during certain stages of infection, and thus point out the putative drug targets. Among others, fatty acid and lipid syntheses reactions are recent targets of new antimicrobial drugs. Genome-scale metabolic models provide an improved understanding of how intracellular pathogens utilize the existing microenvironment of the host. Here, we reviewed the current knowledge of genome-scale metabolic modeling in pathogen cells as well as pathogen host interaction systems and the promising applications in the extension of curative strategies against pathogens for global preventative healthcare.

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Genome-Scale Metabolic Modeling for Unraveling Molecular Mechanisms of High Threat Pathogens.

Biobased products are complete or partial derivatives from naturally occurring/growing materials such as agricultural, plants, and forest materials and serve as an alternative to traditional product derivatives of petroleum. Technically, biobased product counterparts can replace almost every fossil resource-based industrial material. Adopting life cycle analysis and circular economy concepts has also accelerated the move towards biobased products. It meets the criteria for easy recycling and can facilitate the shift from linear fossil-based productions to a greener circular economy. In line with the Renewable and Sustainable Energy Reviews (RSER) policy, this Virtual Special Issue (VSI) published two types of articles, high-quality review papers and original research papers with a strong review component. After a rigorous peer-review process, 32 articles were accepted and published in this VSI. This editorial overview these articles and examines their contribution to the field. This RSER VSI has contributed with new insights on value-added biobased products from various bioresources to their applications, technical challenges and advancement in a sustainable manner. 

Biobased biorefineries: Sustainable bioprocesses and bioproducts from biomass/bioresources special issue

Staphylococcus aureus is a leading cause of biofilm-associated infections, including infective endocarditis, worldwide. A greater understanding of metabolic forces driving biofilm formation in S. aureus is essential for the identification of novel therapeutic targets and for the development of new strategies to combat this medically important pathogen. ABSTRACT Staphylococcus aureus is a medically important pathogen with high metabolic versatility allowing it to infect various niches within a host. S. aureus utilizes two major transcriptional regulators, namely, CodY and CcpA, to remodel metabolic and virulence gene expression in response to changing environmental conditions. Previous studies revealed that inactivation of either codY or ccpA has a pronounced impact on different aspects of staphylococcal physiology and pathogenesis. To determine the contribution and interplay of these two regulators in modulating central metabolism, virulence, and biofilm development, we constructed and characterized the codY ccpA double mutant in S. aureus UAMS-1. In line with previous studies, we found that CcpA and CodY control the cellular metabolic status by altering carbon flux through the central and overflow metabolic pathways. Our results demonstrate that ccpA inactivation impairs biofilm formation and decreases incorporation of extracellular DNA (eDNA) into the biofilm matrix, whereas disrupting codY resulted in a robust structured biofilm tethered together with eDNA and polysaccharide intercellular adhesin (PIA). Interestingly, inactivation of both codY and ccpA decreases biofilm biomass and reduces eDNA release in the double mutant. Compared with the inactivation of codY, the codY ccpA mutant did not overexpress toxins but maintained overexpression of amino acid metabolism pathways. Furthermore, the codY ccpA mutant produced large amounts of PIA, in contrast to the wild-type strain and ccpA mutant. Combined, the results of this study suggest that the coordinated action of CodY and CcpA modulate central metabolism, virulence gene expression, and biofilm-associated genes to optimize growth on preferred carbon sources until starvation sets in. IMPORTANCE Staphylococcus aureus is a leading cause of biofilm-associated infections, including infective endocarditis, worldwide. A greater understanding of metabolic forces driving biofilm formation in S. aureus is essential for the identification of novel therapeutic targets and for the development of new strategies to combat this medically important pathogen. This study characterizes the interplay and regulation of central metabolism and biofilm development by two global transcriptional regulators, CodY and CcpA. We found that the lack of CcpA and/or CodY have different impacts on intracellular metabolic status leading to a formation of morphologically altered biofilms. Overall, the results of this study provide new insights into our understanding of metabolism-mediated regulation of biofilm development in S. aureus.

Interplay of CodY and CcpA in Regulating Central Metabolism and Biofilm Formation in Staphylococcus aureus

Background The role of methane in global warming has become paramount to the environment and the human society, especially in the past few decades. Methane cycling microbial communities play an important role in the global methane cycle, which is why the characterization of these communities is critical to understand and manipulate their behavior. Methanotrophs are a major player in these communities and are able to oxidize methane as their primary carbon source. Results Lake Washington is a freshwater lake characterized by a methane-oxygen countergradient that contains a methane cycling microbial community. Methanotrophs are a major part of this community involved in assimilating methane from lake water. Two significant methanotrophic species in this community are Methylobacter and Methylomonas. In this work, these methanotrophs are computationally studied via developing highly curated genome-scale metabolic models. Each model was then integrated to form a community model with a multi-level optimization framework. The competitive and mutualistic metabolic interactions among Methylobacter and Methylomonas were also characterized. The community model was next tested under carbon, oxygen, and nitrogen limited conditions in addition to a nutrient-rich condition to observe the systematic shifts in the internal metabolic pathways and extracellular metabolite exchanges. Each condition showed variations in the methane oxidation pathway, pyruvate metabolism, and the TCA cycle as well as the excretion of formaldehyde and carbon di-oxide in the community. Finally, the community model was simulated under fixed ratios of these two members to reflect the opposing behavior in the two-member synthetic community and in sediment-incubated communities. The community simulations predicted a noticeable switch in intracellular carbon metabolism and formaldehyde transfer between community members in sediment-incubated vs. synthetic condition. Conclusion In this work, we attempted to predict the response of a simplified methane cycling microbial community from Lake Washington to varying environments and also provide an insight into the difference of dynamics in sediment-incubated microcosm community and synthetic co-cultures. Overall, this study lays the ground for in silico systems-level studies of freshwater lake ecosystems, which can drive future efforts of understanding, engineering, and modifying these communities for dealing with global warming issues.

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Investigation of microbial community interactions between Lake Washington methanotrophs using -------genome-scale metabolic modeling.

Rhodopseudomonas palustris: A biotechnology chassis.

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An integrated computational and experimental studyto investigate Staphylococcus aureus metabolism

Phasins are a particularly fascinating class of small-molecular weight proteins that are the dominant proteins surrounding bioplastic granules produced by bacteria, called polyhydroxyalkanoates (PHAs). PHAs are biopolymers of interest since their thermomechanical properties are comparable to petroleum-based plastics, they are biodegradable, biocompatible, and can be produced from renewable bioresources. As the design and development of sustainable bioproducts from biomass and bioresources is becoming increasingly desirable, efforts to characterize and optimize PHA production have illuminated some exceptional functions of phasins. In addition to their surface performance in PHA granule formation, phasins have been shown to perform chaperone-like activities for bacterial stress mitigation, activate PHA depolymerization, contribute to PHA granule segregation, and boost the expression and activity of PHA synthases. Due to the newfound knowledge of the structures, functions, and strong amphiphilic tendencies of phasins, they have been applied in a wide variety of sustainable applications far beyond bioplastic production. Thus, phasins are emerging as a biotechnology platform for sustainable, next generation bioproduction from biomass. This review provides a synopsis of the biotechnical advances employing phasins, which include optimized bioplastic production, increased tolerance to growth inhibitors in biorefineries, “green” biocatalysis, environmental remediation, and an assortment of sustainable therapeutic bioproducts. Research gaps and suggested applications of phasins are also offered as a potential guide for future direction. • Phasins are the dominant proteins surrounding bioplastic granules inside bacteria. • Phasins have been engineered for applications far beyond that of bioplastics. • Phasins provide a unique strategy to develop novel bioproducts from biomass. • Many phasins are predicted by bioinformatics, but have yet to be verified. • Phasins also perform chaperon activities that help mitigate stress for bacteria. 

http://manuscript.elsevier.com/S1364032122000570/pdf/S1364032122000570.pdf

Biotechnical applications of phasins: Small proteins with large potential

The autonomous mobile robot was designed and implemented which was capable of navigating in the industrial environments and did a job of picking objects from variable height and delivering it to another location following a predefined trajectory. In developing country like Bangladesh industrial robotics is not very prevalent yet, due to the high installation cost. The objective of this project was to develop an autonomous mobile robot for industrial application using the available resources in the local market at lower manufacturing cost. The mechanical system of the robot was comprised of locomotion, gripping and elevation system. Grippers were designed to grip objects of a predefined shape. Cartesian elevation system was designed for vertical movement of the gripper. PIC18F452 microcontroller was the brain of the control system. The prototype autonomous robot was fabricated for relatively lower load than the industry and the performance was tested in a virtual industrial environment created within the laboratory to realize the effectiveness. Keywords—Industrial application; autonomous mobile robot; appropriate technology.

Rajib K. Saha

Papers

Rhodopseudomonas palustris: A biotechnology chassis.

An integrated computational and experimental studyto investigate Staphylococcus aureus metabolism

Biotechnical applications of phasins: Small proteins with large potential

Fabrication of Autonomous Wheeled Mobile Robot for Industrial Applications Using Appropriate Technology

Opening the door to nitrogen fixation in oxygenic phototrophs.