The authors found similar findings to others in the literature that Gram-positive bacteria were more sensitive than Gram-negative bacteria, such as E. coli, potentially due to the outer membrane that surrounds the lipopolysaccharide wall inhibiting the penetration of the hydrophobic phenolic compounds.
To investigate the penetration of the epidermal layer through compound appressoria of F. graminearum laser scanning microscopy was performed.
The high-powered laser degrades most organic compounds, although it enables the penetration of the cuticle layer and the ablation of intra-body materials.
Although Gram positive bacteria lack of outer membrane, the thicker cell wall consist of few peptidoglycan layers could act as functional barrier thus hinder the penetration of antimicrobial compound into the bacterial cell [ 29].
No Americans were killed in the raid, but the attackers' rapid penetration of the compound raised questions about how vulnerable American diplomatic sites may be even after a concerted campaign in recent years to make them more secure.
This suggests an incomplete penetration of the compound; however, increasing the exposure time to BODIPY-taxol from 2 to 6 h produced a relatively homogeneous distribution at this depth (data not shown), similar to that described for the TSWT in Figure 3H.
This compound was used at a concentration which was approximately 50 fold higher than the biochemically measured IC50 (pilot experiments showed this concentration did not produce obvious toxicity) to account for potentially incomplete cell penetration of the compound (although lower concentrations of compound did produce a measurable effect, data not shown).
This was confirmed by the use of ruthenium red to test whether TJ were present, showing that the tracer diffused all the way through the intercellular space until a TJ complex stopped additional penetration of the compound to deeper epithelial layers (Fig. 1C, arrow).
Of course, lead optimization projects in which the key driving factor is phenotypic antitubercular activity can present medicinal chemists with significant challenges in terms of understanding and rationalizing structure activity relationships (SAR), as changes in penetration of the compound may also modulate activity in addition to producing changes in target engagement.
Since the chemical composition of the fungal cells walls is highly lipophilic, they generally represent strong barriers for the penetration of hydrophilic compounds, and the transport of polar compounds through the outer lipid layer of fungi is retarded (Skaltsa et al. 2000).
