Our earth is home to a vast majority of microorganisms which have been an interesting field of study for a period of years. Microorganisms have been proven to be beneficial in many aspects of our lives. Extremophilic microbes are found in the “extreme” environments ranging from the bottom of deep oceans, glacial deserts, and hypersaline environments (Dead Sea) to hot springs. Variety of extremophiles thrive at different environmental conditions; temperature variations, pressure, salinity, pH, radiation by developing molecular mechanisms which stabilizes their proteins, cell membranes, lipids, and nucleic acids. The enzymes derived from these extremophiles led to scientific advancements by their application in the field of biotechnology and industrial fields.

Bacterial pathogens have coevolved with the human host for millions of years. During the course of evolution, the bacterial pathogens have adapted to escape the immunological defense responses of the host and to sustain and survive the action of various antibiotics. The widespread use of antibiotics and the host defense system creates a hostile environment for bacteria during their infection and proliferation stages. Bacteria that are either virulent or multidrug-resistant can fight with one of the two onslaughts, either the host defense or the treatment with antibiotics. The development of antibiotic resistance in bacterial species often results in a fitness cost and mutations associated with it may disrupt essential biological functions. Microbes have developed ways to mitigate this hostile situation in unconventional ways via combining the virulence and resistance mechanisms overcoming the evolutionary trade-offs and compensating for the fitness cost. Bacteria employ mechanisms such as hypermutation, compensatory mutations, cross coselection, antibiotic tolerance and persistence in maintaining antibiotic resistance by offsetting the fitness costs. Such strains are widespread among human infections resulting in huge direct medical costs, morbidity, and causing social distress. In this chapter, the authors discuss the interplay between virulence and resistance with respect to the presented mechanisms in providing an added advantage to bacterial pathogens to adapt in different environments, particularly the infective environment. The biological factors and mechanisms that influence the successful association of resistance and virulence mechanisms are described herein, with accompanying examples for specific virulence and resistance factors in several pathogens. Systematic understanding of mechanisms in bacterial pathogens related to their survival strategies will help direct research toward better treatment and prevention strategies.

Bacteria are the most successful species, primarily because of their survival under unfavorable conditions. They elicit a quick response after sensing the environmental stimuli and generate a response via different signaling modules. The generation of second messengers is one of the most efficient ways to respond to a signal. In this chapter, we have discussed the importance and function of nucleotides as second-messenger signaling molecules in bacteria. We have focused on three molecules— cyclic-di-AMP, cyclic-di-GMP, and (p)ppGpp. In response to different signals, these nucleotides can regulate several processes in bacteria, including transcription, protein synthesis, and replication. Alterations in these processes in turn lead to major morphological changes in bacteria. Here we have discussed the metabolism of these nucleotides and an example of associated changes in bacterial physiology.

Contrary to common understanding, bacterial responses are not standalone. External stimuli trigger bacterial communities to respond in consorted manner. Mega habitats on earth predominantly support biofilms form of growth. Heterogeneous microbial consortia stabilize over matrix and grow on the interface between any two of solid, liquid, or gas. This biofilm is advantageous to bacterial population by supporting nutrient acquisition, its use and recycling along with retention of aqueous microenvironment, enhanced cell-to-cell communication and orchestrated response against stresses like biocides and toxins.

Proteins play a critical role in extremophiles for their survival in extreme environmental conditions. Enzymes, made up of proteins, act as catalyst in biochemical reactions. Enzymes from bacteria, growing in hostile environmental conditions, have high reaction kinetics and facilitate bacterial biochemical reactions at extreme conditions, leading to growth and survival of these bacteria. Whether bacteria fight against host-immune system or adapt to unfavorable conditions (anaerobic, extreme acidic) within or outside the host in the extreme environments, bacterial proteins play an essential role in adapting to hostile conditions. Highly efficient reaction kinetics of these enzymes from extremophiles makes these extremophiles attractive source of proteins for commercial use.

Mycobacterium tuberculosis (Mtb) is an extremely pathogenic bacterium which is responsible for causing tuberculosis. M. tuberculosis generally causes infection in lungs and other organs, can survive different physiological conditions inside the host and can also cause latent infection. Mtb, for its survival and pathogenesis, has to modulate various host pathways. The common pathways that are altered by Mtb include modulation of glycolytic flux, endoplasmic reticulum (EPR) stress, mitochondrial metabolism, apoptosis, and necrosis, inhibition of phagosome maturation and autophagy. Mtb harbors various mechanisms to evade host defense pathways for its survival. There are several types of antiinflammatory microRNA-21 which can help in cadence of glycolytic flux and also regulate the levels of phosphofructokinase by decreasing the biosynthetic precursors which are required for inflammatory responses. Further, the EPR stress pathway can be modulated by Mtb with the help of unfolded protein response–inducible transcription factor C/EBP homologous protein. The necrosis is regulated by inhibiting reactive oxygen species (ROS) production with the help of prostaglandin E2. With the help of extracellular regulated kinase 1/2, signal transducer and activator of transcription 3, and mitogen-activated protein kinase p38, interleukin -10 executes apoptosis pathway. Further, autophagy modulation synthesizes phenolic glycolipid with the help of polyketide synthase, encoded by intact pks 1–15 and by manipulating Ca2+ signaling.

Mycobacterium tuberculosis is foremost public health issues globally, and the emergence of multidrug resistance (MDR) and extensively drug resistance tuberculosis (XDR-TB) has further worsened the situation. Eradication of tuberculosis (TB) has become increasingly difficult due to the acquisition of the remarkable intrinsic mechanisms by M. tuberculosis to counter most of the antibiotics. In addition, adaptive antibiotic resistance in M. tuberculosis is recently characterized mechanisms, which include biofilm-mediated resistance and formation of drug-tolerant persister cells and are responsible for relapse cases of infection. Biofilms are formed by a spectrum of pathogenic microorganisms, and provide a means for these organisms to guard themselves against antimicrobial agents. Bacterial biofilms are the basis of several diseases and mainly attributed to the increased antibiotic resistance unveiled by the microbial communities within the biofilm. The resistance in M. tuberculosis is multifactorial, there are several drug resistance mechanisms exist that act together in order to provide an increased level of resistance to biofilm communities. These mechanisms are based on wild type genes and are not the result of mutations. This chapter summarizes both historical and current scientific data in support of the known biofilm-based resistance and tolerance mechanisms in M. tuberculosis, that can further explore in clinical settings.

Thermophiles are able to grow optimally at relatively higher temperatures. The structural and functional modifications that the thermophilic microorganisms undergo to thrive under high thermal environments are being studied in recent years. This vast domain gives a sheer overview of the art of adaptation of life linked with high temperatures on earth and beyond. Studies have shown the modifications of the cell membrane, proteins, enzymes, and these microbes to fit into such hostile environments and maintain the cell’s function and integrity.

There are variations in the physical and chemical conditions on various places of the earth, and living organisms thrive in every territory. All organisms have an ideal growth condition to thrive and reproduce, which is their optimum growth condition. Some organisms can grow in extreme conditions such as high temperature, high pressure, high radiations, and extreme pH and are known as extremophiles. Extreme conditions are typical for such organisms, and they are biochemically and metabolically active. Radiation damages the genome of the microorganisms and leads to mutation. For their survival, DNA repair mechanism of radio-resistant microorganisms involves several damage repair strategies that involve the extended synthesis-dependent strand annealing and RecF pathway that allows them to repair radioactive damages. Some microorganisms are highly resistant to different types of radiation, known as radio-resistant microorganisms. They have developed various mechanisms like producing mycosporine-like amino acids for survival in high radiation exposure. Understanding the survival mechanisms of these organisms would enlighten the path of evolution and, most importantly, in our quest for extra-terrestrial life.

Microbial biofilm is defined as a group of microorganisms adhered to an animate or inanimate surface through a self-produced exocytosed polymeric substance. The inability of the antimicrobial components to infiltrate the composite biofilm grid or to the make-up of the bacterial arrangement inside the biofilm helps in protecting the microorganisms. Biofilms can protect microorganisms from extremities: high temperature, pH, high saltiness, high pressure, scarcity of nutrients, antibiotics, etc. as a “protective covering.” In an ecological biome, establishment of biofilms has a crucial role in microbial persistence. Biofilms create challenges in manufacturing sectors like water, energy, food, and medicine, as they build up on the food itself and food-processing equipment, contaminating water channels, corroding submerged metal surfaces, and persisting on medical use devices. Biofilm can boost resistance to host protection systems and are projected for implicating persistent infections, surging healthcare expenses, inpatient care rates, sickness, and deaths. Biofilm-related ailments consist of chronic otitis, periodontitis, respiratory diseases, and chronic wound infections. Bacterial cells inhabiting in the interior of a biofilm are resilient to antibiotics, enduring up to 100–1000 fold better than individual cells. The microbiota inhabiting the human gut creates an intricated-interdependent collaboration with epithelial and immune cells of the gastrointestinal tract (GIT). During the course of collaboration, the microbiota provides nourishment, establishes an initial line of security countering invasion by pathogenic organisms, modulating epithelial growth and immune retaliation. When bacterial cells shift to the biofilm mode of growth, it undergoes a phenotypic modification in behavior in which hefty number of genes are differentially regulated. In this chapter, the regulation of certain genes leading to formation of biofilms by different microorganisms is discussed.