TABLE 3.
Mutations identified by WGS in the clones isolated after serial passage in absence and presence of AMPs
| Strain | Serially passaged with | Gene(s) and product(s)a | Location | Typeb | Changec | Potential contribution to resistanced | Reference |
|---|---|---|---|---|---|---|---|
| DA61861 | No AMP | IGR smd_0007 (hypothetical protein) and smd_0008 (periplasmic binding protein TonB) | 10561 | SNP | |||
| smd_2232 (glucan 1,4-alpha-glucosidase) | 2484187 | SNP | Arg468Pro | ||||
| DA61862 | No AMP | IGR smd_3461 (Xaa-Pro dipeptidase) and smd_3462 (Xaa-Pro aminopeptidase) | 3869293 | Del 6 nt | |||
| DA61863 | No AMP | IGR smd_2831 (LacI family transcriptional regulator) and smd_2832 (BolA family transcriptional regulator) | 3154404 | SNP | |||
| DA61754 | LL-37 | IGR btuE2 (glutathione peroxidase) and smd_2762 (hypothetical protein) | 3077698 | SNP | Unknown | ||
| smd_3056 (SIMPL domain-containing protein) | 3395040 | SNP | Synonymous | Unknown | |||
| DA61758 | LL-37 | mraW (rRNA small subunit methyltransferase H) | 733802 | Del 23 nt | Arg170fs | Modification of the expression of resistance-related genes through 16S rRNA methylation | 42, 43 |
| smd_0008 (periplasmic binding protein TonB) | 10820 | Del 27 nt | Pro68_Pro76 Del | Reduced interaction or uptake of LL-37 | 47 – 49 | ||
| DA61759 | LL-37 | mraW (rRNA small subunit methyltransferase H) | 733796 | Del 23 nt | Gln171fs | Modification of the expression of resistance-related genes through 16S rRNA methylation | 42, 43 |
| DA61764 | LL-37 | smd_0947 (putative autotransporter protein) | 1068327 | Del 4 nt | Ala3363fs | Unknown | |
| rluD (ribosomal large subunit pseudouridine synthase D) | 3732065 | SNP | Val130Glu | Unknown | |||
| DA61765 | LL-37 | mraW (rRNA small subunit methyltransferase H) | 734100 | Del 11 nt | Asn274fs | Modification of the expression of resistance-related genes through 16S rRNA methylation | 42, 43 |
| DA61770 | LL-37 | hydG (type IV fimbriae expression regulatory protein PilR) | 3741629 | SNP | Asp223Glu | Regulation of the type IV pilus protein PilA and alteration of membrane permeability | 33, 34 |
| DA61771 | LL-37 | smd_0512 (asparagine synthetase) | 582653 | SNP | Asp489Gly | Unknown | |
| DA61776 | LL-37 | smd_1285 (mercury ion transmembrane transporter) | 1434096 | Del 1 nt | Val49fs | Unknown | |
| DA62005 | PR-39 | sspB (stringent starvation protein B) | 1607077 | SNP | Leu19Pro | Regulation of proteases that might inactivate PR-39 | 50, 52, 53 |
| IGR smd_1828 (cytochrome c) and smmG (Co/Zn/Cd efflux system MFP) | 2018638 | SNP | Potential extrusion of PR-39 | 15, 16, 57 | |||
| DA61990 | PR-39 | sspB (stringent starvation protein B) | 1607179 | SNP | Val53Gly | Regulation of proteases that might inactivate PR-39 | 50, 52, 53 |
| IGR smd_1828 (cytochrome c) and smmG (Co/Zn/Cd efflux system MFP) | 2018638 | SNP | Potential extrusion of PR-39 | 15, 16, 57 | |||
| DA62006 | PR-39 | sspB (stringent starvation protein B) | 1607471 | Ins 1 nt | Stop151Ile | Regulation of proteases that might inactivate PR-39 | 50, 52, 53 |
| IGR smd_1828 (cytochrome c) and smmG (Co/Zn/Cd efflux system MFP) | 2018638 | SNP | Potential extrusion of PR-39 | (15, 16, 57) | |||
| DA61991 | PR-39 | sspB (stringent starvation protein B) | 1607179 | SNP | Val53Ala | Regulation of proteases that might inactivate PR-39 | 50, 52, 53 |
| IGR smd_1828 (cytochrome c) and smmG (Co/Zn/Cd efflux system MFP) | 2018638 | SNP | Potential extrusion of PR-39 | 15, 16, 57 | |||
| DA61992 | PR-39 | sspB (stringent starvation protein B) | 1607179 | SNP | Val53Gly | Regulation of proteases that might inactivate PR-39 | 50, 52, 53 |
| DA61993 | PR-39 | sspB (stringent starvation protein B) | 1607322 | Del 5 nt | Gln102fs | Regulation of proteases that might inactivate PR-39 | 50, 52, 53 |
| IGR smd_1828 (cytochrome c) and smmG (Co/Zn/Cd efflux system MFP) | 2018638 | SNP | Potential extrusion of PR-39 | 15, 16, 57 | |||
| DA61994 | PR-39 | IGR smd_1828 (cytochrome c) and smmG (Co/Zn/Cd efflux system MFP) | 2018638 | SNP | Potential extrusion of PR-39 | 15, 16, 57 | |
| ppa (inorganic pyrophosphatase) | 3912958 | SNP | Gly2Asp | Restoration of the inorganic phosphate ions flow | 10, 79 | ||
| DA61995 | PR-39 | sdhA (succinate dehydrogenase flavoprotein subunit) | 1909333 | SNP | Asp239Gly | Proper functioning of the ETC | 59 – 62 |
| IGR smd_1828 (cytochrome c) and smmG (Co/Zn/Cd efflux system MFP) | 2018638 | SNP | Potential extrusion of PR-39 | 15, 16, 57 | |||
| DA61947 | Colistin | smd_0260 (hypothetical protein) | 314063 | SNP | Arg76Cys | Unknown | |
| lptB (lipopolysaccharide ABC transporter) | 1154448 | SNP | Thr179Pro | Alteration of the membrane LPS content | 29 | ||
| DA61859 | Colistin | wbiI (polysaccharide biosynthesis protein) | 2036869 | SNP | Leu41Pro | Modification of the cell wall/LPS configuration | 31, 32 |
| smd_2876 (hypothetical protein) | 3197529 | SNP | Pro163Ser | Unknown | |||
| DA61948 | Colistin | lptB (lipopolysaccharide ABC transporter) | 1154448 | SNP | Thr179Pro | Alteration of the membrane LPS content | 29 |
| smd_2395 (outer membrane receptor for ferric coprogen and ferric-rhodotorulic acid) | 2656970 | SNP | Asp3Ala | Unknown | |||
| IGR between btuE2 (glutathione peroxidase) and smd_2762 (hypothetical protein) | 3077698 | SNP | Unknown | ||||
| DA61860 | Colistin | ftsW (cell division protein FtsW) | 740818 | SNP | Leu163Val | Modification of the peptidoglycan content | 30, 65 |
| lptB (lipopolysaccharide ABC transporter) | 1154263 | SNP | Stop240Trp | Alteration of the membrane LPS content | 29 | ||
| IGR suhB (inositol-1-monophosphatase) and htpX (probable protease HtpX homolog) | 3216769 | SNP | Unknown | ||||
| IGR suhB (inositol-1-monophosphatase) and htpX (probable protease HtpX homolog) | 3216771 | SNP | Unknown | ||||
| DA62004 | Colistin | sodB (superoxide dismutase) | 1612533 | SNP | Stop193Cys | Defense against hydroxyl radical production by colistin | 80 – 82 |
| rpfG (response regulator) | 2232601 | Ins 6 nt | Glu181_Thr182 Ins ArgGlu | Alteration of expression of membrane/LPS-related genes or alleviation of cellular damage | 39, 40 | ||
| IGR btuE2 (glutathione peroxidase) and smd_2762 (hypothetical protein) | 3077698 | SNP | Unknown | ||||
| DA61989 | Colistin | sodB (superoxide dismutase) | 1612533 | SNP | Stop193Cys | Defense against hydroxyl radical production by colistin | 80 – 82 |
| DA61949 | Colistin | phoQ (sensor protein PhoQ) | 315083 | SNP | Ala30Val | Alteration of LPS modification-related genes | 35 – 38 |
| crp (cyclic AMP receptor protein) | 4370898 | SNP | Arg149Gly | Alteration of expression of membrane/LPS-related genes or alleviation of cellular damage | 41, 83 | ||
| DA61950 | Colistin | smd_0260 (hypothetical protein) | 314136 | SNP | Asp100Gly | Unknown |
a
IGR, intergenic region; MFP, membrane fusion protein.
b
SNP, single-nucleotide polymorphism; Del, deletion; Ins, insertion; fs, frameshift.
c
Stop, stop codon.
d
ETC, electron transport chain; LPS, lipopolysaccharide.