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At least 19 recordsLinked to original sources
PubMed2025

The Mycobacterium tuberculosis Transposon Sequencing Database (MtbTnDB): A Large-Scale Guide to Genetic Conditional Essentiality.

Characterizing genetic essentiality across various conditions is fundamental for understanding gene function. Transposon sequencing (TnSeq) is a powerful technique to generate genome-wide essentiality profiles in bacteria and has been extensively applied to Mycobacterium tuberculosis (Mtb). Dozens of TnSeq screens have yielded valuable insights into the biology of Mtb in vitro, inside macrophages, and in model host organisms. Despite their value, these Mtb TnSeq profiles have not been standardized or collated into a single, easily searchable database. This results in significant challenges when attempting to query and compare these resources, limiting our ability to obtain a comprehensive and consistent understanding of genetic conditional essentiality in Mtb. We address this problem by building a central repository of publicly available Mtb TnSeq screens, the Mtb transposon sequencing database (MtbTnDB). The MtbTnDB is a living resource that encompasses to date ≈150 standardized TnSeq screens, enabling open access to data, visualizations, and functional predictions through an interactive web app (www.mtbtndb.app). We conduct several statistical analyses on the complete database, such as demonstrating that (i) genes in the same genomic neighborhood have similar TnSeq profiles, and (ii) clusters of genes with similar TnSeq profiles are enriched for genes from similar functional categories. We further analyze the performance of machine learning models trained on TnSeq profiles to predict the functional annotation of orphan genes in Mtb. By facilitating the comparison of TnSeq screens across conditions, the MtbTnDB will accelerate the exploration of conditional genetic essentiality, provide insights into the functional organization of Mtb genes, and help predict gene function in this important human pathogen.

DNA Transposable Elements↗
PubMed2026

Applications of transposon-insertion sequencing for understanding bacterial physiology.

Transposon-insertion sequencing (Tn-seq) couples transposon mutagenesis with next-generation sequencing to identify the transposon insertion site for thousands of mutants in parallel. It is a powerful technology with a myriad of uses beyond the identification of essential genes required for a cell to grow and divide. Tn-seq is particularly useful as a high-throughput method to assign function to function-unknown genes, which have increased steadily with the abundance of newly sequenced bacterial genomes. Tn-seq has now been adapted for use in over 100 bacterial species. Here, we summarize the applications of Tn-seq for querying bacterial physiology and discuss some of the possible applications for the future.

DNA Transposable Elements↗
PubMed2026

Transposon insertion sequencing of Pseudomonas aeruginosa identifies multiple intersecting pathways essential for extreme colistin resistance.

Colistin is used to treat antibiotic resistant gram-negative infections, including those caused by Pseudomonas aeruginosa (Pa). Using a diverse collection of clinical isolates, we identified BWH047, a colistin-resistant isolate with an extremely high minimum inhibitory concentration (MIC, 1280 µg/mL). To characterize the genes conditionally essential for colistin resistance in BWH047, we employed transposon insertion sequencing and identified 20 gene candidates. In-frame deletion validated 75% of the candidates and identified genes in several new pathways that contribute to colistin resistance in Pa, including algU and wapH. We also identified several candidate genes from previously reported colistin resistance pathways (e.g., arn, pmrAB). We further investigated the impact of a colistin resistance-associated inner membrane DedA-family undecaprenyl phosphate flippase, which we named DpcA (DedA of Pseudomonas necessary for colistin resistance A). Deletion of dpcA in BWH047 restored sensitivity to colistin (MIC = 0.5 µg/mL) and resulted in several unique changes to the structure of lipopolysaccharide (LPS), including production of decreased amounts of the colistin resistance-conferring 4-amino-4-deoxy-L-arabinose (L-Ara4N) modification on lipid A. This work represents a robust analysis of colistin resistance in Pa and identifies intersecting pathways that contribute to extreme phenotypic resistance.

Pseudomonas aeruginosa↗
PubMed2026

Comparative essentialome analysis of six Pectobacteriaceae strains using the TNSEEK pipeline identifies conserved and strain-specific fitness determinants.

Transposon sequencing (Tn-seq) is a powerful technique for defining the essential genes required for bacterial survival. However, gene essentiality can vary significantly across taxonomic levels, and comparing large Tn-seq datasets from multiple strains presents considerable analytical challenges. To address this, we developed TNSEEK, a fully automated bioinformatics pipeline for the systematic and comparative analysis of Tn-seq experiments. We applied TNSEEK to analyse newly generated data for six soft rot Pectobacteriaceae strains, encompassing species from the Dickeya and Pectobacterium genera, grown in a rich medium. This approach identified a core essentialome of 225 genes, primarily involved in fundamental cellular maintenance, conserved across all 6 strains, a set comparable in size to that of the neighbouring Enterobacteriaceae family. Only a few genus-specific essential genes were found, highlighting interesting distinct metabolic capabilities between Dickeya and Pectobacterium genera. In striking contrast, we discovered a large variable essentialome comprising 181 strain-specific genes, many of which are of unknown function. A portion of these strain-specific essential genes are components of defence systems and prophage genomic regions. The unexpected essentiality of selected components of these modules is consistent with cellular dependency on cognate toxic, restriction or immunity functions encoded by defence-associated loci under the tested growth condition. Furthermore, a comparison with the Escherichia coli essentialome demonstrates that discrepancies in gene essentiality can often be attributed to differences in growth conditions, particularly temperature, as well as variations in genetic redundancy. In conclusion, the TNSEEK pipeline provides a reproducible framework for comparative analysis of mariner/Himar1 Tn-seq datasets across multiple strains.

Pectobacterium↗
PubMed2025

Genome-wide analysis of Enterococcus faecalis genes that facilitate interspecies competition with Lactobacillus crispatus.

Enterococci are opportunistic pathogens notorious for causing a variety of infections. While both Enterococcus faecalis and Lactobacillus crispatus are commensal residents of the vaginal tract, the molecular mechanisms that enable E. faecalis to take advantage of a vaginal biome with lower counts of lactobacilli to colonize the vaginal tract and induce aerobic vaginitis remain unknown. Here, we show that L. crispatus eradicates E. faecalis in a contact-independent manner. Using transposon sequencing to identify E. faecalis OG1RF transposon (Tn) mutants that are either under-represented or over-represented when co-cultured with L. crispatus, we found that Tn mutants with disruption in the dltABCD operon, that encodes the proteins responsible for the D-alanylation of teichoic acids, and OG1RF_11697 encoding for an uncharacterized hypothetical protein are more susceptible to killing by L. crispatus. Inversely, Tn mutants with disruption in ldh1, which encodes for L-lactate dehydrogenase, are more resistant to L. crispatus killing. Using the Galleria mellonella infection model, we show that co-injection of L. crispatus with E. faecalis OG1RF enhances larvae survival while this L. crispatus-mediated protection was lost in larvae co-infected with either L. crispatus and E. faecalisΔldh1 or Δldh1Δldh2 strains. Last, using RNA sequencing to identify E. faecalis genes that are differently expressed in the presence of L. crispatus, we found major changes in the expression of genes associated with glycerophospholipid metabolism, central metabolism, and general stress responses. The findings in this study provide insights into how E. faecalis mitigate assaults by L. crispatus.IMPORTANCEEnterococcus faecalis is an opportunistic pathogen notorious for causing a multitude of infections. As vaginal commensals, E. faecalis must interact with Lactobacillus crispatus, but how E. faecalis overcomes or mitigate assaults by L. crispatus killing remains unknown. We show that L. crispatus eradicates E. faecalis temporally in a contact-independent manner. Using high-throughput molecular approaches, we identified genetic determinants that enable E. faecalis to compete with L. crispatus. This study represents an important first step for the identification of adaptive genetic traits required for enterococci to tolerate assaults by lactobacilli.

Enterococcus faecalis↗
PubMed2025

Identification of sporulation genes in Bacillus anthracis highlights similarities and significant differences with Bacillus subtilis.

The molecular basis of endospore formation in the model gram-positive bacterium Bacillus subtilis has been investigated for over half a century. Here, using high throughput and classical genetic approaches, we performed a comparative analysis of sporulation in the human pathogen Bacillus anthracis. A transposon-sequencing screen identified >150 genes required for B. anthracis sporulation. As anticipated, many of the genes that are critical for sporulation in B. subtilis were also required for B. anthracis sporulation. However, we identified >50 genes that are important for sporulation in B. anthracis but not in B. subtilis, and 22 B. anthracis sporulation genes that are absent from the B. subtilis genome. To validate the hits from our screen, we generated an ordered transposon-mutant library using Knockout Sudoku. Cytological analysis of a subset of the canonical sporulation-defective mutants revealed similar but not identical phenotypes in the pathogen compared to the model. We investigated several of the newly identified sporulation genes, with an in-depth analysis of one, ORF 04167, renamed ipdA. Sporulating cells lacking ipdA are blocked in the morphological process of engulfment, generating septal bulges. An AlphaFold-Multimer screen and a classical genetic enrichment revealed that IpdA is a secreted inhibitor of the polysaccharide deacetylase PdaN. Our data support a model in which induction of IpdA at the onset of sporulation inhibits deacetylation of the cell wall peptidoglycan (PG), enabling the sporulation-specific PG hydrolases to catalyze engulfment. Altogether, our studies reveal that B. subtilis is an excellent model for endospore formation in B. anthracis, while underscoring the importance of direct analysis in B. anthracis. The suite of tools that we have generated will catalyze the molecular dissection of sporulation and other cell biological processes in this important human pathogen.

Bacillus anthracis↗
PubMed2026

Genomic Insights into Mammaliicoccus sciuri from Subclinical Bovine Mastitis to Unveil Key Resistance, Virulence, Biofilm and Adaptation Traits.

The Mammaliicoccus sciuri (M. sciuri), is recognized as a reservoir of antimicrobial resistance (AMR) genes, poses challenges in the Indian dairy sector where antibiotic use is poorly regulated. This study aimed to genomically characterize M. sciuri (formerly Staphylococcus sciuri) isolates recovered from subclinical mastitis (SCM) cattle milk. A total of 128 composite (quarter-wise pooled) milk samples were collected from 199 households (HH) across 16 epiunits /villages in four blocks of Chikkaballapur district, Karnataka, India. Of these, 36 milk samples (28.13%, 36/128; 95% CI: 21.06–36.46%) were diagnosed with SCM using the California Mastitis Test (CMT) and bacteriological culture yielded 113 isolates (88.28%; 113/128; 95% CI: 81.56–92.77%) were phenotypically identified as Staph spp. Through molecular technique PCR targeting the gap gene, two isolates (1.77%; 2/113; 95% CI: 0.49–6.22%) from Hosuru and Gattamaranahalli epiunits were confirmed as M. sciuri and both isolates were mecA-positives indicating methicillin resistance. Whole genome sequencing (WGS) identified 36–37 resistance genes (mecA and blaZ), conferring resistance to β-lactams, macrolides, fluoroquinolones and aminoglycosides. Horizontal gene transfer (HGT) was evidenced by diverse mobile genetic elements (MGEs) such as SCCmec variants, insertion sequences, transposons (IS3, IS6, IS256, and IS1182) and plasmids (Rep1, Rep13, RepUS5 and RepUS43). Virulence profiling uncovered biofilm-associated genes (ica, bap) and heavy metal resistance operons (ars, cop, znu) suggesting mechanisms for environmental persistence and co-selection of resistance traits. Phylogenetic analysis of 99 global isolates revealed host-and geography-specific clustering with Indian isolates occupying distinct evolutionary niches. These findings highlights its possible role as an AMR reservoir and also in bovine mastitis.

Animals↗
PubMed2026

Azotobacter vinelandii gene fitness following carbon shift from sucrose to acetate, succinate and glycerol.

Nitrogen-fixing microbes are a primary contributor of this important nutrient to the global nitrogen cycle. Biological nitrogen fixation (BNF) through the enzyme nitrogenase requires extensive energy that in whole cells is generally studied during the oxidation of carbohydrates such as sugars. The nitrogen-fixing bacterium Azotobacter vinelandii is a model diazotroph for the study of aerobic BNF. Much is known about metabolism in A. vinelandii when cultured on a simple medium where energy is provided primarily in the form of sucrose or glucose. Outside of the laboratory, this soil bacterium grows on metabolites primarily derived from plant root exudates or from the degradation of dead plant matter. In this work, we expand on previous studies looking at genes that are essential to BNF in A. vinelandii when grown on sucrose medium using transposon sequencing (Tn-seq). We applied Tn-seq to determine the genes essential to growth when the medium was shifted to acetate, succinate or glycerol as the primary carbon and energy source to fuel both growth and BNF. A global overview of the genes of central metabolism and those directing substrates toward central metabolism, along with a selection of unexpected genes that were essential for specific growth substrates, is provided.

Azotobacter vinelandii↗
PubMed2025

Cross-species phenotypic profiling uncovers functional determinants of bacterial cold shock adaptation.

Temperature shifts impose broad physiological stress, requiring precise and dynamic regulatory programs to restore cellular homeostasis. While the heat shock response is well characterized, the mechanisms underlying cold shock response (CSR) remain less understood. To identify genes critical for cold adaptation, we applied transposon sequencing (Tn-seq) to monitor mutant fitness across the full course of CSR and sustained low-temperature growth in two mesophilic bacteria, Escherichia coli and Bacillus subtilis. In B. subtilis, phenotypic profiling revealed a temporally structured program: membrane fluidity and cell wall remodeling were most critical in the early stage of CSR, whereas post-transcriptional regulation became essential during late-stage recovery to reprogram gene expression and restore growth. Cross-species comparison uncovered both conserved and species-specific mechanisms, with RNA metabolism and ribosome/translation regulators playing broad roles. Specifically, we identified a conserved synergy between two ribosomal RNA methyltransferases, RsmA and RsmH, in promoting cold adaptation. In B. subtilis, mutants lacking these enzymes exhibited significant delay in translation recovery following cold-induced global inhibition. Together, these findings provide a comparative, systems-level view of bacterial cold adaptation and establish a framework for exploring stress responses in pathogens and extremophiles.

Cell envelope↗
PubMed2025

CRISPRi-mediated repression of three cI repressors induces the expression of three related Neisseria gonorrhoeae bacteriophages.

The Neisseria gonorrhoeae FA1090 isolate encodes nine prophage islands (Ngoɸ1-9). Ngoɸ1-3 contain genes consistent with a Siphoviridae-dsDNA bacteriophage (phage). Saturating transposon-sequencing screens using two different N. gonorrhoeae isolates predicted that multiple prophage genes were essential, including three putative transcriptional repressors: ngo0479 (present in Ngoɸ1), ngo1116 (present in Ngoɸ2), and ngo1630 (present in Ngoɸ3). All three genes display homology to the Lambda phage cI, a regulator important for maintaining the lysogenic state and inhibiting lytic induction, but these proteins are not close paralogs. Using a Neisseria lactamica-derived Type I-C CRISPR-interference system, we show that these cI orthologs are essential, as the knockdown of each gene results in bacterial death. We determined that the repression of the three cI orthologs resulted in the significant induction of phage gene expression. Finally, we detected Siphoviridae-like phage particles released from N. gonorrhoeae following repression of ngo0479, ngo1116, or ngo1630. We hypothesize that these cI orthologs are critical for preventing phage lytic infection and cell death and allow N. gonorrhoeae to benefit from the carriage and expression of prophage genes.IMPORTANCEBacteriophage, or phage, are bacteria-infecting viruses and are the most abundant natural entities in the world. Here, we report that Neisseria gonorrhoeae's three most complete double-stranded DNA prophage islands each encode essential and related transcriptional repressors. CRISPRi-mediated repression of these transcriptional repressors leads to a significant increase in prophage gene expression and phage induction. This study marks an important initial step in studying the interaction between N. gonorrhoeae and its resident phage.

Neisseria gonorrhoeae↗
PubMed1978

Location of ribosome-binding sites on the tetracycline resistance transposon Tn10.

Eight ribosome-binding sites were located on the single-stranded Tn10 DNA loop which was formed after denaturation of lambda phage DNA containing the Tn10 transposon sequence. Ribosomes were bound only to the Tn10 loop contained on the R strand of lambda DNA but not to that on the L strand, suggesting that one of the two strands of Tn10 DNA is selectively transcribed. Six of the eight ribosome binding sites were located in one-half of the DNA loop. The maximum sizes of potential polypeptides were calculated for these genes to range between 9,500 and 84,000 daltons.

Binding Sites↗
PubMed2023

Genome-wide screen in human plasma identifies multifaceted complement evasion of Pseudomonas aeruginosa.

Pseudomonas aeruginosa, an opportunistic Gram-negative pathogen, is a leading cause of bacteremia with a high mortality rate. We recently reported that P. aeruginosa forms a persister-like sub-population of evaders in human plasma. Here, using a gain-of-function transposon sequencing (Tn-seq) screen in plasma, we identified and validated previously unknown factors affecting bacterial persistence in plasma. Among them, we identified a small periplasmic protein, named SrgA, whose expression leads to up to a 100-fold increase in resistance to killing. Additionally, mutants in pur and bio genes displayed higher tolerance and persistence, respectively. Analysis of several steps of the complement cascade and exposure to an outer-membrane-impermeable drug, nisin, suggested that the mutants impede membrane attack complex (MAC) activity per se. Electron microscopy combined with energy-dispersive X-ray spectroscopy (EDX) revealed the formation of polyphosphate (polyP) granules upon incubation in plasma of different size in purD and wild-type strains, implying the bacterial response to a stress signal. Indeed, inactivation of ppk genes encoding polyP-generating enzymes lead to significant elimination of persisting bacteria from plasma. Through this study, we shed light on a complex P. aeruginosa response to the plasma conditions and discovered the multifactorial origin of bacterial resilience to MAC-induced killing.

Humans↗
PubMed2025

A genome-wide screen in ex vivo gallbladders identifies Listeria monocytogenes factors required for virulence in vivo.

Listeria monocytogenes is a Gram-positive pathogen that causes the severe foodborne disease listeriosis. Following oral infection of the host, L. monocytogenes disseminates from the gastrointestinal tract to peripheral organs, including the gallbladder, where it replicates to high densities, establishing the gallbladder as the primary bacterial reservoir. Despite its importance in pathogenesis, little is known about how L. monocytogenes survives and replicates in the gallbladder. In this study, we assessed the L. monocytogenes genes required for growth and survival in ex vivo non-human primate gallbladders using a transposon sequencing approach. The screen identified 43 genes required for replication in the gallbladder, some of which were known to be important for virulence, and others had not been previously studied in the context of infection. We evaluated the roles of 19 genes identified in our screen both in vitro and in vivo, and demonstrate that most were required for replication in bile in vitro, for intracellular infection of murine cells in tissue culture, and for virulence in an oral murine model of listeriosis. Interestingly, strains lacking the mannose and glucose phosphoenolpyruvate-dependent phosphotransferase system (PTS) permeases Mpt and Mpo exhibited no defects in intracellular growth or intercellular spread, but were significantly attenuated during murine infection. While the roles of PTS systems in vivo were not previously appreciated, these results suggest that PTS permeases are necessary for extracellular replication during infection. Overall, this study demonstrates that L. monocytogenes genes required for replication in the gallbladder also play broader roles in disease.

Listeria monocytogenes↗
PubMed2026

Identification of a putative RocS homolog through phenotypic profiling of uncharacterized essential genes in Streptococcus mutans.

Genome-wide viability catalogs produced by transposon sequencing (Tn-seq) and CRISPR interference (CRISPRi) have successfully mapped the essential genome of Streptococcus mutans . In this study, we combined predictive bioinformatics, conditional CRISPRi transcriptional silencing, transmission electron microscopy, transcriptomics, and genetic suppressor screens to investigate nine poorly characterized essential genes in S. mutans . From this screen, phenotypic and genetic analyses identified SMU_393 as a functional homolog of the pneumococcal chromosome segregation factor, RocS. Depletion of SMU_393 resulted in abnormal cell widening, hypersensitivity to DNA damage, and a significant subpopulation of anucleate cells. These phenotypes were bypassed by a spontaneous surface-exposed missense mutation ( dnaA Q197E ) within the AAA+ ATPase domain of the replication initiator. Together, this study refines annotations within the S. mutans essential genome and provides genetic insights into streptococcal chromosome segregation and cell cycle control.

Journal Article↗
PubMed1979

DNA sequence analysis of the transposon Tn3: three genes and three sites involved in transposition of Tn3.

The complete nucleotide sequence of the transposon Tn3 and of 20 mutations which affect its transposition are reported. The mutations, generated in vitro by random insertion of synthetic restriction sites, proved to contain small duplications or deletions immediately adjacent to the new restriction site. By determining the phenotype and DNA sequence of these mutations we were able to generate an overlapping phenotypic and nucleotide map. This 4957 bp transposon encodes three polypeptides which account for all but 350 bp of its total coding capacity. These proteins are the transposase, a high molecular weight polypeptide (1015 amino acids) encoded by the tnpA gene; the Tn3-specific repressor, a low molecular weight polypeptide (185 amino acids) encoded by the tnpR gene; and the 286 amino acid beta-lactamase. The 38 bp inverted repeats flanking Tn3 appear to be absolutely required in cis for Tn3 to transpose. Genetic data suggest that Tn3 contains a third site (Gill et al., 1978), designated IRS (internal resolution site), whose absence results in the insertion of two complete copies of Tn3 as direct repeats into the recipient DNA. We suggest that these direct repeats of complete copies of Tn3 are intermediates in transposition, and that the IRS site is required for recombination and subsequent segregation of the direct repeats to leave a single copy of Tn3 (Gill et al., 1978). A 23 nucleotide sequence within the amino terminus of the transposase which shares strong sequence homology with the inverted repeat may be the internal resolution site.

Base Sequence↗
PubMed2026

Identification of genes promoting fitness of a plant-associated Salmonella Choleraesuis strain on alfalfa sprouts during cold storage.

Consumption of sprouted seeds, such as alfalfa sprouts, has increased in recent years due to their nutritional value and antioxidant content. However, these products have repeatedly been implicated in outbreaks of foodborne pathogens, including Salmonella enterica. Although host-adapted Salmonella serovars are less frequently associated with foodborne illness, infections caused by these serovars often result in invasive and severe outcomes, highlighting the importance of understanding their persistence in food production systems. Moreover, the variability among Salmonella serovars requires characterization beyond the most prevalent types to support the development of precision food safety strategies effective across the diversity of serovars capable of contaminating fresh produce. Here, a plant-internalized Salmonella Choleraesuis strain was used as a model to investigate persistence mechanisms on alfalfa sprouts. A bar-coded transposon mutant library comprising approximately 33,000 unique insertions was generated, along with a collection of individual insertion mutants. These resources were used to identify genetic determinants contributing to strain fitness on sprouts under abusive cold storage (8°C) simulating commercial shelf-life environments. Genome-wide analyses identified negative selection for mutants with insertions in eda, fabF, lpp1_2, pnp, stpA, SCHChr_03621, and two intergenic regions. Competition assays confirmed fitness defects associated with eda, encoding a key enzyme of the Entner-Doudoroff pathway; mnmG, encoding a tRNA modification enzyme involved in translational fidelity; and fabF, involved in fatty acid biogenesis. These findings provide a genome-wide perspective on mechanisms enabling persistence on sprouts of a plant-associated, host-adapted Salmonella strain during cold storage and inform risk assessment and intervention design within precision food safety frameworks.IMPORTANCEFood safety strategies are frequently based on knowledge derived from well-studied, epidemiologically relevant Salmonella serovars, yet many less frequent types still pose a risk to consumers and may contaminate fresh produce. Different Salmonella serovars may vary in the relative contribution of persistence mechanisms. Recognizing these differences is essential for improving precision food safety efforts, particularly for foods such as sprouts that are repeatedly linked to outbreaks. This study highlights that less-studied serovars can rely on both shared survival strategies and unique traits that might otherwise not be captured by current control approaches. By demonstrating that strain diversity influences persistence on fresh produce, this work supports the development of precision food safety strategies that address a broader spectrum of Salmonella, thereby improving risk assessment and helping to better protect public health.

food safety↗
PubMed1979

DNA sequences of the integration sites and inverted repeated structure of transposon Tn3.

The nucleotide sequence of the "inverted repeat" structure of the transposon Tn3 was determined by the DNA sequencing procedure developed by Maxam and Gilbert(1). The sequence, 38 base pairs long, is as follows: 5'-GGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAG..(Tn3) 3'-CCCCAGACTGCGAGTCACCTTGCTTTTGAGTGCAATTC.. The integration of Tn3 is associated with a directly repeated sequence of 5 nucleotides appearing at each end of Tn3. The two directly repeated sequences so far determined are not the same. Furthermore, there is no homologous structure around the integration point of Tn3.

Base Sequence↗
PubMed1979

Multiple forms of inducible drug-metabolizing enzymes: a reasonable mechanism by which any organism can cope with adversity.

All organisms possess a number of genetically regulated mechanisms in order to cope with rapid adverse changes in the environment. The two systems which appear to respond to a seemingly endless array of chemical specificities are the immune response and the induction of drug-metabolizing enzymes. Similarities and differences between the immunoglobulin and the cytochrome P-450-mediated monooxygenase systems are described. DNA insertion sequences, plasmid "transposons," maize "controlling elements," gene duplication, intervening sequences, and high-frequency intergenic recombination are all discussed as possible methods by which organisms can "adapt" quickly to a new selective pressure. If the regulation of P-450 induction resembles in any way the other methods by which pro- and eukaryotes cope genetically with numerous forms of environmental adversity, therefore, it is very likely that mammalian tissues contain hundreds, if not thousands, of inducible forms of P-450.

Adaptation, Physiological↗