An active β‐lactamase is a part of an orchestrated cell wall stress resistance network of Bacillus subtilis and related rhizosphere species

Abstract

Summary A hallmark of the Gram‐positive bacteria, such as the soil‐dwelling bacterium Bacillus subtilis, is their cell wall. Here, we report that d‐leucine and flavomycin, biofilm inhibitors targeting the cell wall, activate the β‐lactamase PenP. This β‐lactamase contributes to ampicillin resistance in B. subtilis under all conditions tested. In contrast, both Spo0A, a master regulator of nutritional stress, and the general cell wall stress response, differentially contribute to β‐lactam resistance under different conditions. To test whether β‐lactam resistance and β‐lactamase genes are widespread in other Bacilli, we isolated Bacillus species from undisturbed soils, and found that their genomes can encode up to five β‐lactamases with differentiated activity spectra. Surprisingly, the activity of environmental β‐lactamases and PenP, as well as the general stress response, resulted in a similarly reduced lag phase of the culture in the presence of β‐lactam antibiotics, with little or no impact on the logarithmic growth rate. The length of the lag phase may determine the outcome of the competition between β‐lactams and β‐lactamases producers. Overall, our work suggests that antibiotic resistance genes in B. subtilis and related species are ancient and widespread, and could be selected by interspecies competition in undisturbed soils.

Functional Genomics Insights Into the Pathogenicity, Habitat Fitness, and Mechanisms Modifying Plant Development of Rhodococcus sp. PBTS1 and PBTS2

“…Soil dwelling microbes typically use antibiotic production, especially ß-lactams, to protect their niche in this nutrient-poor environment. Therefore, successful soil inhabitants often exhibit antibiotic resistances (Butterworth et al, 1979;Bucher et al, 2019). Both PBTS strains appeared to be characterized by a differential set of ß-lactamases ( Supplementary Table S10) and, in agreement with the higher number of putative ß-lactamase genes in PBTS2 compared to PBTS1 (5 versus 2), antibiograms showed that the former was indeed much more resistant to different penicillins (Table 4).…”

Bacillus subtilis Colonization of Arabidopsis thaliana Roots Induces Multiple Biosynthetic Clusters for Antibiotic Production

“…β-lactamases are enzymes that account for an additional layer of defense as they hydrolyze the β-lactam ring of β-lactams, thus inactivating the antibiotic before it reaches its target, the PBPs (penicillin binding proteins) ( Therrien and Levesque, 2000 ). The active β-lactamase of B. subtilis ( Takagi et al., 1993 ; Bucher et al., 2019 ) was not induced but rather modestly decreased ( p = 0.015) in the presence of the plant ( Supplementary Figure S1 ). In addition, the expression of the core metabolic enzyme lactate dehydrogenase ldh was also unaffected by the root ( Supplementary Figure S1 ).…”

“…the PBPs (penicillin binding proteins) (Therrien and Levesque, 2000). The active b-lactamase of B. subtilis (Takagi et al, 1993;Bucher et al, 2019) was not induced but rather modestly decreased (p = 0.015) in the presence of the plant (Supplementary Figure S1). In addition, the expression of the core metabolic enzyme lactate dehydrogenase ldh was also unaffected by the root (Supplementary Figure S1).…”

Weaponizing volatiles to inhibit competitor biofilms from a distance

“…In nature, bacteria form complex and differentiated multicellular communities, known as biofilms 1 . The coordinated actions of many cells, communicating and dividing labour, improve the ability of the biofilm community to resist antibiotics and environmental assaults [2][3][4] . Bacterial biofilms are associated with persistent chronic infections, and thus pose a global threat of extreme clinical importance 5,6 .…”