Microbiology: Bacteria, Viruses, and the Microbial World

Introduction to Microbiology

Microbiology encompasses the study of organisms too small to see with the naked eye: bacteria, archaea, viruses, fungi, algae, and protists. These organisms represent the vast majority of biological diversity and biomass on Earth, driving elemental cycles, shaping animal physiology through the microbiome, causing infectious diseases, and serving as workhorses of biotechnology. Bacteria alone produce half of Earth's oxygen and fix most atmospheric nitrogen—processes underpinning all terrestrial and marine ecosystems.

The germ theory of disease established in the 1880s through Koch's postulates—that specific microorganisms cause specific diseases—revolutionised medicine and public health. Subsequent development of vaccines (smallpox eradication), antibiotics, and antifungals transformed infectious disease from humanity's greatest killer. Yet antimicrobial resistance, emerging pandemics, and neglected tropical diseases remind us that the microbial world remains a persistent challenge requiring ongoing scientific and public health vigilance.

Bacterial Biology

Cell Structure and Diversity

Bacteria lack a nucleus; DNA is in the nucleoid as a single circular chromosome, supplemented by plasmids encoding accessory traits including antibiotic resistance. The cytoplasm contains 70S ribosomes—distinct from eukaryotic 80S, enabling selective antibiotic targeting. Gram-positive bacteria have thick peptidoglycan walls staining purple; Gram-negative bacteria have thin peptidoglycan plus an outer lipopolysaccharide membrane staining pink. This structural difference profoundly affects antibiotic susceptibility—penicillin targets peptidoglycan synthesis; polymyxins disrupt the Gram-negative outer membrane. Flagella, pili, and capsules mediate motility, adhesion, conjugation, and immune evasion.

Metabolism and Growth

Bacterial metabolic diversity vastly exceeds that of eukaryotes. Photoautotrophs (cyanobacteria) fix CO2 via photosynthesis; chemolithotrophs oxidise inorganic compounds (hydrogen, sulfur, iron, ammonia) for energy; diverse heterotrophs metabolise organic compounds aerobically or anaerobically. E. coli in rich broth doubles every 20 minutes; Mycobacterium tuberculosis every 18 hours—explaining why TB treatment takes months. Bacterial growth curves: lag phase (adjustment), log phase (exponential, antibiotic-susceptible), stationary (nutrient-limited), death phase. Persister cells—metabolically dormant subpopulation—survive antibiotics and resume growth after treatment, contributing to chronic infections and relapse.

Microbial Genetics

Horizontal Gene Transfer

Bacteria exchange genetic material through conjugation (direct cell-to-cell plasmid transfer), transformation (uptake of environmental naked DNA—exploited to transform competent E. coli with plasmids in molecular biology), and transduction (bacteriophage-mediated gene transfer). These mechanisms enable rapid spread of antibiotic resistance genes between unrelated species. Resistance plasmids carrying multiple resistance determinants spread through clinical bacteria globally—the same plasmid encoding carbapenem resistance was isolated from patients in different countries within months of its emergence. Horizontal gene transfer drives bacterial evolution far faster than mutation and drift alone.

Quorum Sensing

Quorum sensing is bacterial population-density-dependent gene regulation through diffusible chemical autoinducers. As autoinducer concentration exceeds a threshold when population is dense, population-wide gene expression shifts to coordinate behaviours advantageous only at high density: biofilm formation, bioluminescence in Vibrio fischeri (marine squid symbiosis), and virulence factor secretion in Pseudomonas aeruginosa and Staphylococcus aureus. Blocking quorum sensing—quorum quenching using signal-degrading enzymes or receptor antagonists—is a promising anti-virulence strategy that avoids selecting for conventional antibiotic resistance.

The Human Microbiome

The human body hosts trillions of microorganisms. Gut microbiome composition influences immunity, metabolism, mood (gut-brain axis via vagal nerves and short-chain fatty acid signalling), and drug metabolism. Dysbiosis correlates with obesity, inflammatory bowel disease, type 2 diabetes, allergies, autism spectrum disorder, and depression. Faecal microbiota transplantation (FMT) treats recurrent Clostridioides difficile infection with over 90% efficacy by restoring ecological competition preventing C. diff expansion. Probiotic and prebiotic interventions modulate microbiome composition; the therapeutic potential across metabolic and immune conditions is under intense investigation.

Examples and Applications

Example 1: MRSA Resistance Mechanisms

Methicillin-resistant Staphylococcus aureus (MRSA) acquired the mecA gene (on mobile genetic element SCCmec) encoding an alternative penicillin-binding protein (PBP2a) with low affinity for all beta-lactam antibiotics, conferring broad resistance. Community-MRSA strains spread beyond hospitals, causing skin infections and sometimes severe pneumonia in otherwise healthy people. Vancomycin is the last reliable beta-lactam alternative; vancomycin-intermediate S. aureus (VISA) emerging from cell wall thickening shows the inexorable progression of resistance evolution when antibiotics are used extensively.

Example 2: CRISPR Immune Function in Bacteria

CRISPR-Cas systems evolved as adaptive immunity against bacteriophages. When bacteria survive phage infection, short phage DNA sequences are integrated into chromosomal CRISPR arrays. These sequences are transcribed into crRNAs guiding Cas nuclease to cleave matching phage sequences upon re-infection, providing sequence-specific immunity. The diversity of CRISPR-Cas systems across bacteria classifies into multiple types with different nuclease architectures. Understanding CRISPR's natural function in bacterial immunity provided the conceptual and molecular foundation for its development as a gene editing tool.

Example 3: Biofilm Formation

Biofilms—structured communities of bacteria adhered to surfaces and enclosed in extracellular matrix—are 100-1000x more resistant to antibiotics than planktonic bacteria. Biofilm matrix (polysaccharides, proteins, DNA) impedes antibiotic penetration; slow growth reduces antibiotic activity; persister cells in biofilms tolerate transient antibiotic exposure and repopulate after treatment. Biofilms cause chronic infections in implanted medical devices (catheters, prosthetic joints, heart valves), cystic fibrosis lung infections (P. aeruginosa), and chronic wounds. Developing anti-biofilm strategies—dispersal agents, matrix-degrading enzymes, quorum quenching—is a research priority.

Example 4: Clostridium difficile and FMT

C. difficile colitis occurs when antibiotic use disrupts normal gut microbiome, allowing this toxin-producing anaerobe to overgrow. Toxins A and B disrupt intestinal epithelial cell cytoskeleton causing colitis; severe cases can be fatal. Standard treatment (vancomycin or fidaxomicin) has 15-25% recurrence rate as the microbiome recovers incompletely. FMT—infusing donor stool (capsules or colonoscope) restoring a diverse microbial community—achieves over 90% cure rates in recurrent cases and is approved treatment, demonstrating that ecological approaches complement antibiotic treatment for dysbiosis-driven diseases.

Example 5: Mycobacterium tuberculosis Pathogenesis

Mycobacterium tuberculosis persists in alveolar macrophages by preventing phagosome-lysosome fusion—a remarkable intracellular survival strategy. Dormancy mechanisms allow survival in granulomas for decades; immunosuppression (HIV, anti-TNF biologics) may trigger reactivation. MDR-TB (resistant to isoniazid and rifampicin) and XDR-TB (further resistant to fluoroquinolones and injectables) require months of toxic multi-drug therapy with limited efficacy. New drugs (bedaquiline, delamanid) targeting unique mycobacterial pathways (ATP synthase, mycobacterial-specific electron transport) offer hope for shorter, more effective TB treatment regimens.

Example 6: Streptococcal Virulence

Streptococcus pyogenes (group A strep) causes pharyngitis, impetigo, and invasive disease. M protein—a major virulence factor—creates an anti-phagocytic surface; its enormous diversity (over 200 M types) prevents broad immunity. Superantigens activate large fractions of T cells non-specifically, causing toxic shock syndrome. Post-streptococcal autoimmune complications (rheumatic fever, glomerulonephritis) arise weeks after infection through molecular mimicry or immune complex deposition. Rheumatic fever remains a leading cause of acquired heart disease in developing countries due to inadequate antibiotic treatment of strep throat—a preventable disease with clear pathogenic understanding.

Example 7: Bacteriophage Therapy

Bacteriophages infecting and killing specific bacterial species are being reconsidered as antibacterial agents as antibiotic resistance worsens. Phage therapy must overcome multiple challenges: phage host specificity requires knowing the pathogen's phage susceptibility; bacteria rapidly evolve resistance to phages; phage immune clearance reduces half-life. Successful compassionate use cases—phage therapy curing MDR Acinetobacter baumannii or prosthetic device infections—sparked renewed clinical interest. Engineered phages with expanded host range or carrying anti-resistance genes represent next-generation approaches. Phage banks and rapid susceptibility testing are being developed.

Example 8: Extremophile Industrial Enzymes

Extremophile microorganisms from hot springs, acid mines, and deep-sea vents produce enzymes stable under conditions that denature mesophilic proteins. Taq polymerase from Thermus aquaticus (Yellowstone hot spring thermophile) revolutionised PCR by enabling amplification at high temperatures without adding fresh enzyme. Alkaline proteases from alkaliphilic bacteria are detergent industry workhorses for laundry washing at high pH and temperature. Amylases from thermophiles convert starch to glucose in food and biofuel industries. Extremophile enzyme discovery continues providing industrial process advantages and expanding our understanding of life's biochemical boundaries.

Try it live

Everything above runs in your browser — open Bacterial Growth & Phage Infection Simulator and change the parameters while it is running. Nothing is installed, nothing is uploaded, the whole model lives in one tab.