Table 2 Noteworthy genes or loci absent in the  M. ulcerans  MRCA

selA

MMAR_5190

selenocysteine synthase, required for the synthesis of proteins containing selenocysteine.

[1]

MMAR_5194 MMAR_5195

Formate dehydrogenase alpha and beta subunits, selenocysteine-containing. Likely role in anaerobic growth.

[1]

MMAR_2615

Anaerobic dehydrogenase (putative nitrate reductase), possible role in anaerobic growth.

lgt

MMAR_2416

Lgt acylates prolipoproteins, thus key role in lipoprotein synthesis. Lgt mutant of S. aureus is less immunogenic.

[45–47]

plcB_2,

MMAR_1485

M. marinum has six plc genes. Four of these are absent in all M. ulcerans. Phospholipase C enzymes can cause direct or indirect enzymatic hydrolysis of host cell membrane phospholipids and appear important for mycobacterial intracellular survival.

[48]

plcB_5,

MMAR_3656

plcB_6,

MMAR_4722

plcB_3

MMAR_0284

cstA

MMAR_1616

Carbon starvation protein, CstA. In E. coli, cstA encodes a peptide transporter and is induced by carbon starvation. Maybe part of a redundant stress response system in M. ulcerans.

[49]

cueO

MMAR_1618

Multicopper oxidases protect against oxidative stress. This enzyme has functions in tolerance to copper, and iron and manganese oxidation in a range of bacteria. It catalyses the oxidation of cuprous copper, ferrous iron and diphenolic compounds. In Salmonella, a cueO deletion mutant is less virulent in mouse model. Divergent transcriptional arrangement with cstA.

[50]

idsB1,

MMAR_3212

Catalyzes the trans-addition of three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate which is a precursor of the ether-linked lipids. Impact here of diverting all isoprenoid biosynthesis to the non-mevalonate pathway is not known. Possibly more favourable energetically if spending cellular resources on mycolactone synthesis.

[1]

idsB2,

MAR_3219

idsA1

MMAR_5095