Table 1 Examples of studies that reported/predicted phage-mediated alteration of metabolic function in prokaryotic hosts

Vibrio cholera

VPIΦ and CTXΦ; Lysogenic

Insertion of VPIΦ results in toxin-coregulated pilus (TCP) expression; TCP-facilitated CTXIΦ insertion into host genome

(O) Expression of cholera toxin

[67, 68]

Escherichia coli

933 W; Lysogenic to lytic switch

Induction of 933 W prophages that encode for both shiga toxin (Stx) and a cleavable repressor

(O) Greatly increases stx gene expression, and therefore bacterial production and release of Stx.

[65]

Staphylococcus aureus

Φ13; Lysogenic

Integration of Φ13 genome with beta-toxin gene (hlb)

(O) Loss of beta-toxin expression (Note: beta-toxin is a sphingomyelinase)

[71]

Escherichia coli

λ; Lysogenic

λ cI protein expression; cI binds to pckA regulatory region preventing transcription

(O) Suppression of phosphoenolpyruvate carboxykinase production & gluconeogenesis; reduced growth rate; predation avoidance

[66]

Vibrio harveyi 645; 20; 45

VHML; Lysogenic

Integration of VHML genome via transposition

(O) Broad suppression of substrate utilization; changes in d-gluconate utilization (625); c-glutamyl transpeptidase activity (20); and sulfatase activity (45)

[69, 70]

Listonella pelagia

ΦHSIC; Pseudolysogenic

Chromosomal integration of prophage

(O) Reduction in substrate utilization

[21, 110]

Cellulophaga baltica MM#3

ΦS_M and ΦS_T; Lytic

On evolution of phage resistance: possible adaptation of amino acid transporters (likely phage receptors) in cell membrane

(O) Reduction in ability to metabolise various carbon sources, including many amino acids

[111]

Synechococcus WH8109

Cyanophage Syn9; lytic

Phage encoded carbon metabolism genes cp12, talC, psbA, zwf, gnd, and nrdA/nrdB, co-expressed in early infection; two-fold increase in NADPH/NADP ratio

(P) ‘light reactions’ decoupled from ‘dark reactions; ATP & NADPH directed away from the Calvin Cycle. likely towards phage dNTP biosynthesis

[10]

Synechococcus WH8017

S-SM2; lytic

Phage encodes genes for photosynthesis (PSII): psbA; psbD, and carbon metabolism genes: gnd; tal; zwf; CP12

(P) Photosynthesis augmented during infection; carbon redirected from glucose and amino acid production to ribose-5P and NAPDH generation (for dNTP synthesis), via PPP-mediated glucose reduction

[42, 53]

Cyanobacteria: various Prochlorococcus and Synechococcus strains

Various: 42 cultured cyanophages

88% of cyanophage genomes include psbA; 50% code for both psbA and psbD (PSII genes)

(P) Boost to phototrophic metabolism during infection.

[33]

Cyanobacteria

Un-cultured cyanophages

Phage-encoded photosystem I genes psaA, B, C, D, E, K and JF (from environmental samples)

(P) Channelling of reducing power from respiratory chain towards PSI, possibly for ATP generation

[34]

Prochlorococcus MIT9515

P-TIM68; lytic

Phage encoded photosystem I and II proteins incorporated into host membrane

(O) Photosynthetic capacity maintained; enhanced cyclic electron flow around PSI; (P) Generation additional ATP for phage replication

[37]

Vibrios (including V. parahaemolyticus

KVP40; lytic

Phage ORFs code for: PhoH; putative pyridine nucleotide (NAD⁺) salvage pathway, and hydrolysis of NADH

(P) Facilitates cross-membrane transport of NAD⁺ precursors, NAD⁺ synthesis, and cycling of NADH back to precursors.

[112]

Various (marine metagenomic Assemblages)

Various (marine viral metagenomes)

Most abundant putative viral-encoded enzymes: riboreductases; carboxylyases and transferases; psbA genes.

(P) Aids scavenging of host nucleotides (e.g. Riboreductases); supports host metabolism during the infection cycle (e.g., carboxylyases; transferases and D1 protein)

[113]

Various: from 22 ‘ultra-clean’ viromes in POV dataset

Various; classified via protein cluster (PC) generation

35 carbon pathway AMGs, representing a near-full central carbon metabolism gene complement.

(P) In oligotrophic environments, AMGs may redirect host carbon flux into energy production and the replication of viral DNA.

[53]

Various: from 32 viromes in POV dataset

Various; classified via PC generation

32 new viral AMGs (9 core; 20 photic; 3 aphotic): 9 encode Fe-S cluster proteins and genes associated with DNA replication initiation (DnaA), DNA repair (dut; radA) and motility augmentation (psel).

(P) Fe-S cluster modulation may drive phage production (in the photic zone); Genes associated with DNA replication and repair, and motility augmentation could assist high-pressure deep-sea survival.

[30]

Various: 127 SAGs from uncultivated SUP05 bacteria

Various: 69 viral contigs (from SUP05 SAGs)

4 putative AMGs (encoded by 12 viral contigs): phoH (on a bona fide viral contig); 2OG; 2OG-FeII oxygenase, tctA (protein domain only); and dsrC.

(P) dsrC likely functional in SUP05 sulfur cycling; characterisation of viral DsrC needed to elucidate roles of viruses in modulating electron transfer during viral infection.

[16]

Various: Actinobacteria, proteobacteria (α; δ; γ) Bacteroidetes, Cyanobacteria, Deferribacteres

Various, inc. members of T4 (superfamily) and T7 (genus)

243 putative AMGs (95 previously known [6]) including dsrC (11 genes), soxYZ (4 genes), both originating from T4 superfamily; P-II (encodes a nitrogen metabolism regulator) and amoC (encodes ammonia monooxygenase sub-unit)

(P) Viral roles in: Sulfur oxidation, via Dsr and Sox pathways; Nitrogen cycling (influenced by P-II), with potential for alternative pathways of N and NH₃ uptake during N starvation, and NH₃oxidation (via amoC).

[47]

Various: 113 genomes (marine bacteria)

Various: 64 pro-phage-like elements (21 GTAs)

High relative incidence of transcriptional regulatory and repressor-like proteins in putative prophages (comparison: lytic phages)

(P) Suppresses non-essential host metabolic activities in unfavourable environments/periods

[21]

Listeria monocytogenes

‘A118-like prophage’ (reversible excision)

comK gene, encoding L. monocytogenes competence system master regulator, is activated by the excision of A118-like prophage

(O) A118-like prophage is excised only when a L. monocytogenes cell is engulfed by a phagosome: the host’s activated competence system facilitates escape, after which prophage reintegrate with host comK gene, deactivating host’s competence system

[74]

Anabaena spp.; Nostoc spp.

Non-infective ‘prophages’ (x 3; non-reversible excision)

Recombinases (prophage-encoded) act to excise prophages from 3 host genes that are involved in nitrogen fixation (nifD; fdxN; hupL)

(O) In low nitrogen environments, excision of prophages from host N-fixation genes enables conversion of host cell to form nitrogen-fixing heterocysts

[74]

Synechococcus elongatus

Cyanophage AS-1

Prevents normal ppGpp accumulation under nutrient limitation, and the corresponding expression of genes for starvation survival

(O) Inhibits the host’s natural starvation response under nutrient limitation; (P) promotes metabolic activity otherwise undertaken only when food is plentiful, facilitating phage production in low nutrient conditions

[14, 114]