Abstract
Cystic Fibrosis (CF) airways favor abnormal microbial development. Infections are considered as polymicrobial and competition can be observed between microorganisms. The current literature on bacterial competition in CF mostly consists of studies with limited numbers of strains, mainly focused on the major pathogens Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) and does not give a comprehensive overview of the overall importance of bacterial interactions or the behavior of less often encountered emerging bacteria such as Achromobacter. In this context, we screened a panel of 39 strains from six CF patients, of either clinical or domestic environmental origin, distinguished according to genotype and belonging to four opportunistic pathogens, Pa (n = 15), Sa (n = 3), Stenotrophomonas maltophilia (Sm, n = 10) and Achromobacter xylosoxidans (Ax, n = 11). We investigated their capacity to compete in terms of growth, motility, and pigment production on agar media through 203 crossing experiments. Eleven strains selected via the initial screening results were further studied for competitive growth in liquid medium and biofilm formation. Competition was noted for 33% (67/203) of the pairs of strains with 85 modifications observed between monocultures and co-cultures, impacting growth (23.6%), motility (13.8%), and/or pigment production (6.1%). Under all conditions of the study (clinical, environmental strains; intra-, inter-patients; intra-, inter-species levels), competition was significantly more frequent among pairs of strains with at least one clinical strain. While Pa mainly outcompeted other species, in one patient with chronic colonization by Ax and sporadic colonization by Pa, we showed that some Ax inhibited the growth and pigmentation of Pa whereas biofilm formation was drastically reduced. Enlarging the panel of strains tested in competition assays gave new perspectives on the complex interactions taking place among the CF airway community. Indeed, the frequent occurrence of varied, strain-dependent interactions is revealed here. We report the first results of competition assays for Ax with the ability of certain strains to outcompete Pa. Our results are linked to the patient’s colonization history and question the importance of bacterial competitiveness in the colonization pattern of CF airways.
Highlights
Cystic fibrosis (CF) is a genetic disease caused by a mutation in the Cystic Fibrosis Transmembrane conductance Regulator gene coding for a transmembrane channel allowing the transport of chloride ions
The strains under study were isolated during routinely performed analyses of sputum samples from six CF patients (Patients A–F among whom Patients A, C, and F were three patients chronically colonized by A. xylosoxidans included from previous studies (Dupont et al, 2015, 2016, 2018) in which they were known as Patients 12, 2, and 5, respectively) attending the CF center at Montpellier University Hospital, France (n = 24) or from the domestic environment of three of these patients (n = 15; Table 1)
As P. aeruginosa (Pa)–S. aureus (Sa) co-isolation is common in CF, a majority of studies have focused on these opportunistic pathogens (Baldan et al, 2014; Filkins et al, 2015; Hotterbeekx et al, 2017; Limoli et al, 2017; Tognon et al, 2017) whereas fewer studies have addressed the question of interactions between Pa and other bacteria such as members of the Burkholderia cepacia complex (Al-Bakri et al, 2004; Schwab et al, 2014; Bragonzi et al, 2012; Smalley et al, 2015) and various members of the commensal microbiota of the cystic fibrosis respiratory tract (CFRT) (Shinzato and Saito, 1994; Sibley et al, 2008; Whiley et al, 2014; Gao et al, 2018)
Summary
Cystic fibrosis (CF) is a genetic disease caused by a mutation in the Cystic Fibrosis Transmembrane conductance Regulator gene coding for a transmembrane channel allowing the transport of chloride ions. Different organs are affected, including the respiratory tract, where thickening mucus, mucociliary clearance defects, and a decrease in anti-microbial defenses are observed These alterations allow a variety of microorganisms, of endogenous and environmental origin, to multiply in the cystic fibrosis respiratory tract (CFRT; Burns et al, 1998; Lyczak et al, 2002; Ciofu et al, 2013). Pulmonary infections in CF patients have been considered as polymicrobial for more than a decade (Sibley et al, 2006; Peters et al, 2012; O’Brien and Welch, 2019) and pulmonary exacerbations have been shown to be associated with modifications in the CF community and a disruption/fragmentation of bacterial networks observed during stable clinical status (Quinn et al, 2016) These microbiotadisease associations must be interpreted in an ecological perspective as they take place in the pulmonary environment, i.e., a restricted space subjected to diverse selective pressures (immune system, acidic environment, antibiotic cures, etc.; Rogers et al, 2013)
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