Facultative Anaerobes

Overview

Facultative anaerobes are microorganisms—primarily bacteria—that possess the metabolic flexibility to grow in both the presence and absence of oxygen. These organisms can switch between aerobic respiration, anaerobic respiration, and fermentation depending on oxygen availability. When oxygen is present, they preferentially engage in aerobic respiration to generate ATP more efficiently. In hypoxic or anoxic conditions, they adapt by utilizing alternative electron acceptors such as nitrate or sulfate, or by undergoing fermentation. This adaptability allows facultative anaerobes to colonize a broad range of host environments, including inflamed, oxygen-depleted, or necrotic tissues. Many clinically important pathogens are facultative anaerobes, and their role in host tissue invasion, immune evasion, and persistent infection highlights their significance in disease pathogenesis.

Examples of Pathogenic Facultative Anaerobes

Metabolic Flexibility

Facultative anaerobes possess the ability to shift their metabolic strategies based on the availability of oxygen, enabling them to thrive in a wide range of host environments. Under high oxygen conditions, they preferentially utilize aerobic respiration, a highly efficient process that yields approximately 38 ATP per glucose molecule by using molecular oxygen as the terminal electron acceptor. This pathway supports rapid growth and energy production when oxygen is abundant. However, in low-oxygen or anoxic environments—such as inflamed or necrotic tissues—these organisms switch to anaerobic respiration or fermentation, generating between 2 to 36 ATP per glucose, depending on the substrates available. Anaerobic respiration involves the use of alternative electron acceptors such as nitrate, sulfate, or fumarate, while fermentation relies on substrate-level phosphorylation without an electron transport chain. This metabolic flexibility is a key survival advantage, allowing facultative anaerobes to persist and proliferate in variable or oxygen-limited microenvironments commonly found in dysbiotic or inflamed tissues.

Microbiome Context

Facultative anaerobes often dominate the gut microbiota during early-life colonization and are frequently overrepresented in disease states characterized by dysbiosis, mucosal inflammation, and epithelial barrier disruption. Their presence is associated with a shift away from obligate anaerobe dominance typically seen in healthy microbiota, often driven by oxygen gradient disruptions resulting from inflammation or epithelial damage. This altered microenvironment favors facultative species, which can outcompete strict anaerobes and further destabilize the microbial community. In the context of microbiome signatures, the enrichment of facultative anaerobes is a recurring feature in inflammatory and dysbiotic states, indicating that their expansion may serve as both a marker of disrupted host-microbe homeostasis and a driver of disease progression. Their persistence is often linked to tissue oxygenation changes, immune evasion strategies, and metabolic flexibility, especially in conditions where barrier function is impaired and oxygen becomes more bioavailable in typically anaerobic niches.

Association Between Facultative Anaerobes and Nickel

There is a well-established association between facultative anaerobic bacteria and nickel, primarily through the use of nickel-dependent enzymes and metal acquisition systems that support survival, metabolic flexibility, and virulence in oxygen-variable environments. Many clinically significant facultative anaerobes—such as Escherichia coli, Klebsiella pneumoniae, Salmonella spp., and Yersinia pestis—encode enzymes like [NiFe]-hydrogenases and ureases, which require nickel as a cofactor for function. These enzymes are often critical under anaerobic or microaerobic conditions, allowing these organisms to generate energy or neutralize host-derived reactive oxygen species. To support these processes, many facultative pathogens express high-affinity nickel transport systems, such as the NikABCDE complex, to scavenge nickel in low-metal environments like inflamed or damaged host tissues. This reliance on nickel is particularly relevant in microbiome contexts where facultative anaerobes are enriched, such as in chronic inflammatory conditions marked by epithelial barrier disruption and localized hypoxia. The co-occurrence of facultative anaerobes and nickel-utilizing mechanisms in disease-associated microbiome signatures suggests a functional metallomic shift that may be both a marker and driver of pathogenesis. This association supports the rationale for microbiome-targeted interventions that limit nickel availability—such as dietary nickel restriction via low-nickel diets, or chelation therapies—to selectively suppress pathogenic facultative anaerobes while preserving healthy microbial communities.

Mechanistic Link Between Facultative Anaerobes and Nickel

Facultative anaerobes often inhabit environments with fluctuating oxygen levels, such as the gastrointestinal tract, wounds, or inflamed tissues, where oxygen availability is restricted or dynamically altered. In such settings, these organisms rely on anaerobic respiration or fermentation, both of which may involve nickel-dependent enzymatic pathways that are not required under fully aerobic conditions. Most nickel-dependent facultative anaerobes encode specific high-affinity nickel transporters, such as NikABCDE, to acquire nickel in low-metal environments like host tissues. These systems are tightly regulated and are often induced during infection or anaerobic growth.

Key Nickel-Dependent Enzymes in Facultative Anaerobes: