High iron availability | Tobramycin | ↓ | Increased biofilm formation | [21] |
| Tobramycin, colistin, polymyxin B, ciprofloxacin | ↓ | Increased Psl production, changed biofilm structure and enhanced antibiotic tolerance | [22, 23] |
Mucus |
Mucins | Tobramycin, colistin, polymyxin B, levofloxacin, aztreonam, ceftazidim | ↓ | Antibiotic binding through charge and/or hydrophobic interactions | [24–26] |
Gentamicin, β-lactam antibiotics | ↓ | Higher viscosity Lower diffusion rate | [27] |
Aminoglycosides, colistin, polymyxin B, norfloxacin, ciprofloxacin, β-lactam antibiotics | ↓ | Induction of expression of resistance genes | [28] |
Tobramycin | ↓ | Increased biofilm formation | [29] |
Extracellular DNA | Tobramycin | ↓ | Charge interaction Higher viscosity, leading to lower antibiotic diffusion | [30, 31] |
Aminoglycosides, colistin, polymyxin B | ↓ | Mg2+ sequestration and acidification, leading to LPS modification | [32, 33] |
Actin | Tobramycin, colistin | ↓ | Higher viscosity, leading to lower antibiotic diffusion | [34] |
Anoxia | Aminoglycosides | ↓ | Low metabolism | [35–37] |
β-lactam antibiotics | ↓ | Higher expression of efflux pumps | [38, 39] |
Tobramycin | ↓ | Increased alginate production | [40–43] |
Colistin | ↑ | Low metabolism leads to inactivation of adaptive resistance mechanisms | [38, 39] |
Nutritional environment |
Low glucose levels, high amino acid levels | Tobramycin, ciprofloxacin | ↓ | Development of auxotrophy and co-occurrent LasR mutations | [44–46] |
High glucose levels | Ofloxacin | ↓ | Promotion of biofilm formation by inducing Psl production | [47, 48] |
NaCl content and pH | | | |
High NaCl content | Tobramycin, streptomycin | ↑ | Reduced alginate binding | [49, 50] |
| Colistin, ciprofloxacin | ↑ | Synergism | [51, 52] |
Acidic pH | Tobramycin, ceftazidim, ciprofloxacin | ↓ | Induction of biofilm formation | [53] |
Immune response |
LL-37 | Gentamicin, ciprofloxacin | ↓ | Upregulation of multidrug efflux pumps | [54] |
Lactoferrin | Tobramycin | ↓ | Depolarization of bacterial membrane, leading to less antibiotic uptake | [55] |
IL-1 β, IL-6, IL-17 and neutrophil elastase | Aspecific | ↓ | Induction of mucin production | [56] |
Itaconaat | Aspecific | ↓ | Induction of biofilm formation through EPS formation | [57] |
ROS | Aspecific | ↓ | Increased alginate production | [58] |
Higher oxidation level of mucins, leading to less antibiotic diffusion | [59, 60] |
Higher occurrence of hypermutators, which is linked to higher occurrence of persisters | [61] |
Aminoglycosides | ↓ | Induction of efflux pump gene expression | [62] |
Reduced membrane potential and modification of LPS | |